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1.
Article in Chinese | WPRIM | ID: wpr-1028081

ABSTRACT

Objective To investigate the value of histone deacetylase 3(HDAC3)in evaluating the risk of slow/no reflow in AMI patients after PCI.Methods A total of 280 AMI patients undergo-ing PCI in our hospital from June 2020 to June 2022 were recruited,and according to TIMI blood flow grading,they were divided into slow/no reflow group(TIMI≤grade 11,n=54)and normal flow group(TIMI>grade Ⅱ,n=226).The demographic characteristics,underlying diseases,baseline data at admission,and preoperative results of coronary angiography and laboratory tests were compared between the two groups.Multivariate logistic regression analysis was used to determine the influencing factors for slow/no reflow in AMI patients after PCI,and ROC curve was drawn to analyze the predictive value of related indicators for slow/no reflow.Results Obvi-ously larger proportions of smoking history and Killip grade Ⅱ,higher heart rate,longer reperfu-sion time,and higher serum levels of LDL-C,NLR,D-D and HDAC3 were observed in the slow/no reflow group than the normal flow group(P<0.05,P<0.01).Multivariate logistic regression analysis showed that reperfusion time,NLR and HDAC3 were influencing factors for slow/no reflow in AMI patients after PCI(P<0.05,P<0.01).The AUC value of reperfusion time+NLR in predicting the slow/no reflow after PCI in AMI patients was 0.798(95%CI:0.664-0.922,P=0.002),with a sensitivity and specificity of 0.87 and 0.73,respectively.And when serum HDAC3 level was combined in the prediction,the AUC value was 0.903(95%CI:0.790-0.922,P<0.01),with a sensitivity and specificity of 0.93 and 0.84,respectively.Conclusion Preoperative HDAC3 level is an influencing factor for slow/no reflow in AMI patients after PCI.Based on reperfusion time and NLR,combination of the 3 indicators can provide additional predictive value for slow/no reflow in these patients.

2.
Tianjin Medical Journal ; (12): 44-50, 2024.
Article in Chinese | WPRIM | ID: wpr-1020968

ABSTRACT

Objective To construct an in vitro"metabolic memory"cell model of HT-22 mouse hippocampal neurons induced by high glucose,and to investigate the effect of"metabolic memory"on apoptosis and histone acetylation in HT-22 cells.Methods HT-22 cells were cultured in high glucose medium(glucose concentration was 55 mmol/L)and conventional glucose medium(glucose concentration was 25 mmol/L),and cells were divided into the control group(NG 4,6 and 8 groups,25 mmol/L glucose was cultured for 4,6 and 8 days,respectively),the high glucose group(HG 4,6 and 8 groups,respectively)and the metabolic memory group(HG2NG2,HG2NG4,HG2NG6,HG4NG2 and HG4NG4 groups,high glucose culture for 2 days to 25 mmol/L glucose culture for 2,4 or 6 days,high glucose culture for 4 days to 25 mmol/L glucose culture for 2 or 4 days).Cell viability was detected by CCK-8 method.The release of lactate dehydrogenase(LDH)in cell culture supernatant was detected,and the optimal time to establish a"metabolic memory"model was selected.Subsequently,cells were divided into the NG4 group,the NG8 group,the HG4 group,the HG4NG4 group and the HG8 group,and the cell morphology of each group was observed by optical microscope.The apoptosis rate was detected by flow cytometry.The activities of deacetylase(HDAC)and histone acetyltransferase(HAT)were detected by enzyme-linked immunosorbent assay(ELISA).Western blot assay was used to detect expression levels of histone deacetylase 4(HDAC4),B lymphocyte tumor 2(Bcl-2),Bcl-2 related X protein(Bax)and Caspase-3 protein.Results The HG4NG4 group was the ideal cell model with high glucose metabolic memory.Cells of the NG4 group and the NG8 group were interwoven into a dense network,growing well,with spindle shaped cells and distinct synaptic structures.However,in the HG4 group and the HG8 group,the cell body became round,synaptic structure disappeared and growth was inhibited.In the HG4NG4 group,the number of cells increased but their morphology was damaged.Results of flow cytometry showed that compared with the NG8 group,the apoptosis rates were significantly increased in the HG8 group and the HG4NG4 group(P<0.05).ELISA results showed that compared with the NG8 group,the expression levels of HDAC4,Bax,and Caspase-3 proteins increased in the HG8 group and the HG4NG4 group,while the expression level of Bcl-2 protein significantly decreased(P<0.05).Compared with the HG8 group,there were no significant differences in protein expression levels of HAT and HDAC in the HG4NG4 group.Western blot reslts showed that compared with the NG8 group,the levels of HDAC4,Bax and Caspase-3 protein increased in the HG8 group and the HG4NG4 group(P<0.05).Compared with the HG8 group,there were no significant differences in protein expression levels in the HG4NG4 group.Conclusion HT-22 mouse hippocampal neurons cultured with 55mmol/L high glucose for 4 days,and then cultured with 25 mmol/L glucose for 4 days are the ideal"metabolic memory"cell model.The mechanism may be related to the increased activity of HDAC,HAT and HDAC4 expression in the hyperglycemic model.

3.
Acta cir. bras ; Acta Cir. Bras. (Online);39: e392324, 2024. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1556677

ABSTRACT

Purpose Patients have been severely suffered from cancer associated pain, and pancreatic cancer is the most severe form of cancer associated with pain. There are very few options available to manage it. The present report evaluated the effect of 5HT2A on pancreatic cancer associated pain. Methods Pancreatic cancer was induced by injecting SW 1,990 cells (~3×106 in a 20 µL suspension) into the pancreas and formed a 2­3-mm vesicle using an inoculator fitted with a 26-gauge needle in BALB/c-nu mice. Survival rate and body weight of the mice were observed. Pain behaviour testing was performed at the end of each week (third and fourth week) after surgery. Inflammatory mediators and HDAC 2 proteins were determined in the spinal tissue using quantitative real-time polymerase chain reaction. Results There was improvement in the survival rate and body weight in 5HT2A antagonist treated group than pancreatic cancer group of mice. Moreover, 5HT2A antagonist ameliorated the alteration in pain behaviour of pancreatic cancer mice. mRNA expression of HDAC2 and level of inflammatory cytokines were reduced in the spinal tissue of 5HT 2A antagonist treated group than pancreatic cancer group of mice. Conclusions Data revealed that 5HT2A antagonist ameliorates pain associated with pancreatic cancer mice by HDAC inhibition and inflammatory cytokines. The result of investigation supports that modulation of 5HT2A receptor could be used clinically to protects neuropathic pain in pancreatic cancer.


Subject(s)
Animals , Rats , Pain , Pancreatic Neoplasms , Cytokines , Serotonin 5-HT2 Receptor Antagonists , Histone Deacetylases , Animals, Laboratory
4.
Chinese Pharmacological Bulletin ; (12): 2216-2221, 2023.
Article in Chinese | WPRIM | ID: wpr-1013679

ABSTRACT

Acute lung injury ( ALI) and its most extreme form a-cute respiratory distress syndrome ( ARDS) are lung diseases with high morbidity and mortality. There is no effective therapeutic intervention until now for its complicated pathophysiologi-cal processes and sophisticated regulatory mechanism. Histone deacetylases (HDACs) are a family of proteins with deacetylase activity. Studies have shown that HDACs are involved in the pathophysiological processes of ALI/ARDS, including inflammatory responses,endothelial permeability,oxidative stresses,alveolar fluid clearance and lung tissue repairment. Simultaneously, the use of HDACs inhibitors (HDACIs) can interfere with ALI/ ARDS progression. In this review we describe and summarize the pathophysiological processes and the underlying mechanisms in ALI/ARDS regulated by HDACs and HDACIs in detail, in order to provide the basis for the clinical application of HDACs-targe- ted agents and indicate directions for future study.

5.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1536155

ABSTRACT

La giardiasis es la enfermedad gastrointestinal de mayor incidencia mundial, causada por el protozoario Giardia duodenalis, para la cual no se cuenta con una vacuna o tratamiento eficiente. En aras de buscar nuevos blancos farmacológicos contra este parásito, se han estudiado las enzimas del metabolismo energético, como las sirtuinas, deacetilasas dependientes del dinucleótido de adenina y nicotinamida (NAD). Previamente se identificó a GdSir2.1 y GdSir2.2 como deacetilasas dependientes de NAD, con localizaciones subcelulares diferentes. En este trabajo se estudió otro candidato a sirtuina (GdSir2.3) mediante herramientas bioinformáticas para la identificación de características típicas de la familia sirtuina en la secuencia del candidato, y experimentales como la obtención de la proteína recombinante 6xHis-GdSir2.3 que demostró actividad deacetilasa dependiente de NAD y que sirvió como antígeno en la producción de los IgY - α -6xHis-GdSir2.3 para la localización subcelular de la proteína endógena en G. duodenalis. Lo anterior concuerda con otros estudios donde se señala a GdSir2.3 como un importante regulador de la enquistación, debido a su aumento de expresión durante esta etapa del ciclo de vida, constituyéndola como un blanco farmacológico promisorio para el control de esta parasitemia.


Giardiasis is the gastrointestinal disease with the highest incidence worldwide, caused by the protozoan Giardia duodenalis, for which there is no vaccine or efficient treatment. In order to find new pharmacological targets against this parasite, energy metabolism enzymes such as sirtuins, deacetylases dependent on the nicotinamide adenine dinucleotide (NAD), have been studied. GdSir2.1 and GdSir2.2 were previously identified as NAD-dependent deacetylases, with different subcellular locations. In this work, another candidate for sirtuin (GdSir2.3) was studied using bioinformatic tools for the identification of typical characteristics of the sirtuin family in the sequence of the candidate; and experimental ones such as obtaining the recombinant protein 6xHis-GdSir2.3 that demonstrated NAD-dependent deacetylase activity; and that it served as an antigen in the production of IgY - α - 6xHis-GdSir2.3 for the subcellular localization of the endogenous protein in G. duodenalis. The foregoing is consistent with other studies where GdSir2.3 is indicated as an important regulator of encyst due to its increased expression during this stage of the life cycle, constituting it as a promising drug target for the control of this parasitaemia.


A giardíase é a doença gastrointestinal de maior incidência no mundo, causada pelo protozoário Giardia duodenalis, para a qual não existe vacina ou tratamento eficaz. Com o objetivo de encontrar novos alvos farmacológicos contra esse parasita, têm sido estudadas enzimas do metabolismo energético, como as sirtuínas, desacetilases dependentes do dinucleotídeo adenina nicotinamida (NAD). GdSir2.1 e GdSir2.2 foram previamente identificados como desacetilases dependentes de NAD, com diferentes localizações subcelulares. Neste trabalho, outro candidato a sirtuin (GdSir2.3) foi estudado usando ferramentas de bioinformática para a identificação de características típicas da família sirtuin na sequência do candidato; e experimentais, como a obtenção da proteína recombinante 6xHis-GdSir2.3 que demonstrou atividade desacetilase dependente de NAD; e que serviu como antígeno na produção de IgY - α - 6xHis-GdSir2.3 para a localização subcelular da proteína endógena em G. duodenalis. O exposto é consistente com outros estudos em que o GdSir2.3 é apontado como um importante regulador de encisto devido à sua expressão aumentada durante esta fase do ciclo de vida, constituindo-se como um alvo promissor para o controle dessa parasitemia.

6.
Article in Chinese | WPRIM | ID: wpr-957511

ABSTRACT

Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in reduction of intestinal ischemia-reperfusion (I/R) injury by sodium butyrate in mice.Methods:Twenty-four SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) by the random number table method: sham operation group (S group), intestinal I/R group (I/R group), intestinal I/R + sodium butyrate group (I/R+ SB group), and intestinal I/R + ITSA-1+ sodium butyrate group (I/R+ I+ SB group). The model of intestinal I/R injury was established by clipping superior mesenteric artery for 45 min followed by 120 min of reperfusion in anesthetized animals.In I/R+ I+ SB group, the HDACs activator ITSA-1 0.5 mg/kg was intraperitoneally injected at 6, 3 and 1 days before ischemia.Sodium butyrate 500 mg/kg was given by intragastric administration every day one week before ischemia in I/R+ SB group and I/R+ I+ SB group, and the equal volume of normal saline was given in S group and I/R group.At 120 min of reperfusion, the mice were sacrificed and their small intestine tissues were obtained.The levels of diamine oxidase (DAO) in serum and intestinal tissues were detected by enzyme-linked immunosorbent assay.The pathological changes of small intestinal tissues were observed with a light microscope, and intestinal damage was assessed and scored according to Chiu.The expression of microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ), P62 and HDAC6 was determined by Western blot.The contents of histone H3 (H3) and acetylated histone H3 (Ac-H3) in small intestinal tissues were determined by enzyme-linked immunosorbent assay. Results:Compared with S group, the Chiu′s score, levels of DAO in serum and small intestinal tissues were significantly increased, the expression of LC3 Ⅱ and HDAC6 was up-regulated, P62 expression was down-regulated, H3 content was increased, and AC-H3 content was decreased in I/R group ( P<0.05). Compared with I/R group, the Chiu′s score, levels of DAO in serum and small intestinal tissues were significantly decreased, the expression of LC3 Ⅱ and HDAC6 was down-regulated, P62 expression was up-regulated, H3 content was decreased, and AC-H3 content was increased in I/R+ SB group ( P<0.05). Compared with I/R+ SB group, the Chiu′s score and levels of DAO in serum and small intestinal tissues were significantly increased, the expression of LC3 Ⅱ and HDAC6 was up-regulated, P62 expression was down-regulated, H3 content was increased, and AC-H3 content was decreased in I/R+ I+ SB group ( P<0.05). Conclusions:Sodium butyrate can alleviate intestinal I/R injury by inhibition of HDAC6 activity in mice, and the mechanism may be related to inhibition of autophagy and promotion of H3 acetylation.

7.
Article in Chinese | WPRIM | ID: wpr-957551

ABSTRACT

Objective:To evaluate the role of histone deacetylase (HDAC) in sodium butyrate-induced reduction of intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with oxidative stress and cell apoptosis.Methods:Twenty-four SPF healthy male C57BL mice, aged 6-8 weeks, weighing 22-25 g, were divided into 4 groups ( n=6 each) according to the random number table method: sham operation group (S group), intestinal I/R group (IR group), intestinal I/R+ sodium butyrate group (IN group) and intestinal I/R+ ITSA-1+ sodium butyrate group (INI group). In IR, IN and INI groups, the superior mesenteric artery was clamped for 45 min, followed by reperfusion for 2 h to prepare the model of intestinal I/R injury, while the superior mesenteric artery was only isolated without ligation in S group.One week before preparation of the model, sodium butyrate 500 mg/kg was intragastrically administered once a day in IN group and INI group, the HDAC activator ITSA-1 0.5 mg/kg was intraperitoneally injected three times a week in INI group, and the equal volume of normal saline was given instead in the other groups.The mice were sacrificed at 2 h of reperfusion and small intestinal tissues were obtained for microscopic examination of the pathological changes which were assessed using Chiu′s score and for determination of the content of MDA (by enzyme-linked immunosorbent assay) and expression of cleaved caspase-3 (by Western blot). Results:Compared with S group, Chiu′s score was significantly increased, and the expression of cleaved caspase-3 was up-regulated in IR, IN and INI groups, the content of MDA in small intestinal tissues was significantly increased in IR and INI groups ( P<0.05). Compared with IR group, Chiu′s score was significantly decreased in IN and INI groups, and the content of MDA was significantly decreased, and the expression of cleaved caspase-3 was down-regulated in IN group ( P<0.05). Compared with IN group, Chiu′s score and content of MDA were significantly increased, and the expression of cleaved caspase-3 was up-regulated in INI group ( P<0.05). Conclusions:HDAC is involved in sodium butyrate-induced reduction of intestinal I/R injury in mice, which is related to the inhibition of oxidative stress and cell apoptosis.

8.
Article in Chinese | WPRIM | ID: wpr-911248

ABSTRACT

Objective:To evaluate the effect of sirtuin 3 (SIRT3) overexpression on hypoxia-reoxygenation (H/R) injury to hippocampal neurons of mice exposed to high glucose and its relationship with SOD2.Methods:The normally cultured HT22 neurons at the logarithmic phase were selected and divided into 3 groups ( n=12 each) using a random number table method: high-glucose normoxia group (HG group), high glucose+ H/R group (HHR group) and high glucose+ H/R+ SIRT3 overexpression group (HHR+ SIRT3 group). To establish high glucose model, the neurons in 3 groups were cultured in high-glucose culture medium (glucose concentration of 50 mmol/L) for 8 h. In HHR and HHR+ SIRT3 groups, the cells were exposed to glucose-free and hypoxia for 6 h and then cultured in the high-glucose normoxic environment for 24 h to establish the high glucose and HR injury model.In HHR+ SIRT3 group, the neurons were transfected with SIRT3 overexpressed lentivirus.The cell viability was recorded by the cell counting kit-8 assay, reactive oxygen species (ROS) content was detected by flow cytometry, mitochondrial malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, catalase (CAT) activity and adenosine triphosphate (ATP) content were determined by colorimetry, mitochondrial membrane potential (MMP) was detected by JC-1 probe, and the expression of nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), SIRT3, SOD2 and acetylated SOD2 (ac-SOD2) was detected by Western blot. Results:Compared with HG group, cell viability, SOD activity, CAT activity, ATP content, MMP, NRF1 and the expression of TFAM and SIRT3 were significantly decreased, and ROS content, MDA content and ac-SOD2/SOD2 ratio were increased in group HHR and group HHR+ SIRT3 ( P<0.05). Compared with HHR group, cell viability, SOD activity, CAT activity, ATP content, MMP, NRF1 and the expression of TFAM and SIRT3 were significantly increased, and ROS content, MDA content and ac-SOD2 /SOD2 ratio were decreased in HHR+ SIRT3 group ( P<0.05). Conclusion:SIRT3 overexpression can alleviate hypoxia-reoxygenation (H/R) injury to hippocampal neurons of mice incubated in high glucose medium, and the mechanism is related to activation of SOD2 deacetylation.

9.
Chinese Journal of Anesthesiology ; (12): 1238-1241, 2021.
Article in Chinese | WPRIM | ID: wpr-911350

ABSTRACT

Objective:To evaluate the role of histone deacetylase 6 (HDAC6) in spinal dorsal horn in dexmedetomidine-induced reduction of neuropathic pain (NP) in rats.Methods:Forty clean-grade healthy male Sprague-Dawley rats, aged 7-9 weeks, weighing 190-240 g, were divided into 5 groups ( n=8 each) using a random number table method: control group (group C), sham operation group (group SH), group NP, dexmedetomidine group (group D), and specific HDAC6 inhibitor ACY-1215 plus dexmedetomidine group (group AD). The animals were commonly fed without any treatment in group C. The sciatic nerve was only isolated but not ligated in group SH.The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.NP was induced by chronic constrictive injury (CCI). The right sciatic nerve was exposed, and 4 loose ligatures were placed on the sciatic nerve at 1-mm intervals with 4-0 silk thread in NP and D groups.In group D, dexmedetomidine 40 μg/kg was intraperitoneally injected once a day starting from the end of operation until the animals were sacrificed.In group AD, ACY-1215 25 mg/kg was intraperitoneally injected every day immediately before CCI, and dexmedetomidine 40 μg/kg was intraperitoneally injected daily after CCI until 15 days after CCI.The equal volume of solvent was given instead of dexmedetomidine in S and NP groups.The mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (baseline, T 0) and 3, 6, 9, 12 and 15 days after CCI (T 1-5). The rats were then sacrificed, and the dorsal horn tissues of L 4-6 spinal cord were obtained for determination of the expression of myeloid differentiation factor 88 (MyD88) and nuclear factor kappa B (NF-κB) p65 by Western blot. Results:Compared with group C and group SH, the MWT was significantly decreased, and the TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was up-regulated in NP, D and AD groups ( P<0.05). Compared with group NP, the MWT was significantly increased, and the TWL was prolonged at T 1-5, the expression of MyD88 and NF-κB p65 in the spinal dorsal horn was down-regulated in group D ( P<0.05), and no significant change was found in the parameters mentioned above in group AD ( P>0.05). Compared with group D, MWT was significantly decreased, and TWL was shortened at T 1-5, and the expression of MyD88 and NF-κB p65 was up-regulated in the dorsal horn of the spinal cord in group AD ( P<0.05). Conclusion:HDAC6 in spinal dorsal horn is involved in dexmedetomidine-induced reduction of NP in rats, which is related to inhibiting MyD88/NF-κB signaling pathway.

10.
Chinese Journal of Anesthesiology ; (12): 1252-1255, 2021.
Article in Chinese | WPRIM | ID: wpr-911353

ABSTRACT

Objective:To evaluate the role of histone deacetylase 3 (HDAC3) in high glucose hypoxia/reoxygenation (H/R) injury to primary rat cardiomyocytes and the relationship with autophagy.Methods:The primary cardiomyocytes extracted from newborn Sprague-Dawley rats, aged about 1-3 days, were divided into 5 groups ( n=24 each) according to the random number table method: control group (C group, glucose concentration 5.5 mmol/L), H/R group, high glucose group (H group, glucose concentration 30 mmol/L), high glucose H/R group (HH/R group), and high glucose H/R + HDAC3 inhibitor RGFP966 group (HH/R+ RG group). Fifty percent glucose injection was used to prepare high-glucose medium (final concentration 30 mmol/L). Cells were cultured in a hypoxic environment (5% CO 2-0.9% O 2-94.1% N 2) for 6 h, followed by reoxygenation in a normoxic environment for 2 h to establish the cardiomyocyte H/R model in H/R group.RGFP966 at a final concentration of 10 μmol/L was added at 24 h before H/R in HH/R+ RG group.At 2 h of reoxygenation, the cell viability was measured using CCK-8 kit, the activity of lactic dehydrogenase (LDH) in the cell supernatant was determined using enzyme-linked immunosorbent assay, the level of autophagy was detected with a confocal microscope after cells were transfected with autophagy double-labeled adenovirus (mRFP-GFP-LC3), and the expression of HDAC3, p62, LC3 Ⅱ and LC3 Ⅰ was detected using Western blot.LC3Ⅱ/LC3Ⅰ ratio was calculated. Results:Compared with group C, the cell viability was significantly decreased, and the activity of LDH in supernatant was increased in H/R and H groups, the number of autophagosomes was significantly increased, the expression of HDAC3 in cardiomyocytes was up-regulated, the expression of p62 was down-regulated, and the LC3 Ⅱ/I ratio was increased in group H/R, and the number of autophagosomes was significantly decreased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was decreased in group H ( P<0.05). Compared with group H/R, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, the number of autophagosomes was decreased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was decreased in group HH/R ( P<0.05). Compared with group H, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, the number of autophagosomes was increased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was increased in group HH/R ( P<0.05). Compared with group HH/R, the cell viability was significantly increased, the activity of LDH in supernatant was decreased, the number of autophagosomes was increased, the expression of HDAC3 and p62 in cardiomyocytes was down-regulated, and the LC3 Ⅱ/I ratio was increased in group HH/R+ RG ( P<0.05). Conclusion:Up-regulation of HDAC3 expression is involved in high glucose H/R injury to primary rat cardiomyocytes, which is related to decreasing the level of autophagy.

11.
Chinese Journal of Nephrology ; (12): 911-917, 2021.
Article in Chinese | WPRIM | ID: wpr-911912

ABSTRACT

Objective:To investigate the role and mechanism of (histone deacetylase 6, HDAC6) in the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the activation of renal interstitial fibroblasts.Methods:Human renal tubular epithelial cells (HK-2) and rat renal interstitial fibroblast (NRK-49F) were cultured in vitro, and divided into 4 groups: control group, Tubastatin A (TA) group (treated with 10 μmol/L HDAC6 inhibitor TA for 36 h), transforming growth factor-β1 (TGF-β1) group (10 ng/ml TGF-β1 for 36 h), and TGF-β1+TA group (treated with 10 ng/ml TGF-β1 and 10 μmol/L TA for 36 h). The expression levels of fibronectin, α-smooth muscle actin (α-SMA), collagen I, E-cadherin, HDAC6, acetyl histone H3, histone H3, acetyl α-tubulin, α-tubulin, TGF-β receptor (TGF-βR) 1, p-Smad3, Smad3, connective tissue growth factor (CTGF), epidermal growth factor receptor (EGFR) and p-EGFR in HK-2 and NRK-49F cell samples were detected by Western blotting, and quantitative analysis was performed according to gray level. Results:(1) In HK-2 cells stimulated by TGF-β1, TA decreased the expression of fibronectin, α-SMA, collagen I, and increased the expression of epithelial cell marker E-cadherin. Meanwhile, TA decreased the expression of HDAC6 and increased the expression levels of acetyl histone H3 and acetyl α-tubulin (all P<0.05). (2) Compared with the TGF-β1 group, the expressions of TGF-βR1, p-Smad3, CTGF and p-EGFR in TGF-β1+TA group were decreased (all P<0.05), while the total protein levels of Smad3 and EGFR were not significantly different (both P>0.05). (3) In NRK-49F cells stimulated by TGF-β1, TA decreased the expressions of fibronectin, α-SMA, collagen I, TGF-βR1 and p-Smad3 (all P<0.05). Conclusions:Blockade of HDAC6 by TA may inhibit the EMT of renal tubular epithelial cells and the activation of renal interstitial fibroblasts via regulating multiple signaling pathways including TGF-β/Smad3, CTGF and EGFR.

12.
Chinese Journal of Biotechnology ; (12): 2645-2657, 2021.
Article in Chinese | WPRIM | ID: wpr-887830

ABSTRACT

Lysine acetylation is one of the major post-translational modifications and plays critical roles in regulating gene expression and protein function. Histone deacetylases (HDACs) are responsible for the removal of acetyl groups from the lysines of both histone and non-histone proteins. The RPD3 family is the most widely studied HDACs. This article summarizes the regulatory mechanisms of Arabidopsis RPD3 family in several growth and development processes, which provide a reference for studying the mechanisms of RPD3 family members in regulating plant development. Moreover, this review may provide ideas and clues for exploring the functions of other members of HDACs family.


Subject(s)
Arabidopsis/metabolism , Histone Deacetylases/metabolism , Histones , Plant Development/genetics
13.
Braz. j. infect. dis ; Braz. j. infect. dis;24(2): 150-159, Mar.-Apr. 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132431

ABSTRACT

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Quinazolines/pharmacology , Azepines/pharmacology , Virus Activation/drug effects , HIV Infections/virology , HIV-1/drug effects , Niacinamide/pharmacology , Methyltransferases/antagonists & inhibitors , Piperazines/pharmacology , Leukocytes, Mononuclear/virology , CD4-Positive T-Lymphocytes , Gene Expression Regulation, Viral , Virus Latency , Viral Load/drug effects , Viral Tropism/drug effects
14.
Acta Pharmaceutica Sinica B ; (6): 2374-2383, 2020.
Article in English | WPRIM | ID: wpr-881118

ABSTRACT

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity. For the first time, we used the

15.
Journal of Clinical Hepatology ; (12): 1388-1391, 2019.
Article in Chinese | WPRIM | ID: wpr-779121

ABSTRACT

Hepatic ischemia-reperfusion injury has always been a difficult problem in liver transplantation and liver tumor resection. The involvement of multiple mechanisms makes it particularly complex, among which energy expenditure during ischemia and oxidative stress induced by reperfusion are the main mechanisms leading to hepatic ischemia-reperfusion injury and may cause cell death and even liver failure. Silent information regulators are a class of nicotinamide adenine dinucleotide-dependent deacetylases which can lead to deacetylation of transcription factors including histones and nonhistones, and they are playing an important regulatory role in cell apoptosis, inflammatory response, energy balance, and oxidative stress. There are 7 types of silent information regulators in mammals, i.e., Sirt1-Sirt7, among which Sirt1 can reduce hepatocyte stress, regulate cell metabolic pathways, and thus alleviate the degree of hepatic ischemia-reperfusion injury through various signaling pathways. This article reviews the role of Sirt1-related signaling pathways in hepatic ischemia-reperfusion injury.

16.
Mem. Inst. Oswaldo Cruz ; 114: e190366, 2019. tab, graf
Article in English | LILACS | ID: biblio-1101272

ABSTRACT

BACKGROUND Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.


Subject(s)
Animals , Female , Pregnancy , Spleen/chemistry , Schistosomiasis mansoni/metabolism , Breast Feeding , Histone Deacetylases/metabolism , Animals, Suckling/parasitology , Pregnancy Complications, Parasitic , Disease Models, Animal , Immunity, Maternally-Acquired , Animals, Suckling/metabolism
17.
Biol. Res ; 52: 20, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011422

ABSTRACT

BACKGROUND: Histone acetylation is an important epigenetic modification that regulates gene activity in response to stress. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). The imperative roles of HDACs in gene transcription, transcriptional regulation, growth and responses to stressful environment have been widely investigated in Arabidopsis. However, data regarding HDACs in kenaf crop has not been disclosed yet. RESULTS: In this study, six HDACs genes (HcHDA2, HcHDA6, HcHDA8, HcHDA9, HcHDA19, and HcSRT2) were isolated and characterized. Phylogenetic tree revealed that these HcHDACs shared high degree of sequence homology with those of Gossypium arboreum. Subcellular localization analysis showed that GFP-tagged HcHDA2 and HcHDA8 were predominantly localized in the nucleus, HcHDA6 and HcHDA19 in nucleus and cytosol. The HcHDA9 was found in both nucleus and plasma membranes. Real-time quantitative PCR showed that the six HcHDACs genes were expressed with distinct expression patterns across plant tissues. Furthermore, we determined differential accumulation of HcHDACs transcripts under salt and drought treatments, indicating that these enzymes may participate in the biological process under stress in kenaf. Finally, we showed that the levels of histone H3 and H4 acetylation were modulated by salt and drought stress in kenaf. CONCLUSIONS: We have isolated and characterized six HDACs genes from kenaf. These data showed that HDACs are imperative players for growth and development as well abiotic stress responses in kenaf.


Subject(s)
Stress, Physiological/physiology , Hibiscus/enzymology , Histone Acetyltransferases/physiology , Droughts , Histone Deacetylases/physiology , Transcriptional Activation/physiology , Cloning, Molecular , Hibiscus/growth & development , Hibiscus/physiology , Real-Time Polymerase Chain Reaction
18.
Article in Chinese | WPRIM | ID: wpr-751697

ABSTRACT

The occurrence and progress of tumor is the result of the interaction of heredity and epigenetics. Histone deacetylation modification,as an important epigenetic modification,plays an important role in tumorigenesis and development. The abnormal expression of histone deacetylase in normal tissues and cells promotes the development of tumor and is related to the proliferation and apoptosis,angiogenesis,metastasis and drug resistance of tumor cells,and becomes a new target of tumor therapy. Histone deacetylase inhibitors as anti-tumor drugs have a good prospect of application.

19.
Article in Chinese | WPRIM | ID: wpr-754191

ABSTRACT

Objective To investigate the effect and mechanism of suberoylanilide hydroxamic acid (SAHA) on the fear extinction in mice with chronic social defeat stress (SD). Methods Fifty-six male C57BL/6J mice aged 7-8 weeks were randomly divided into control group,social defeat group,control-SAHA group and social defeat-SAHA group to investigate the effect of SAHA and social defeat group,social defeat-AAV BDNF group and social defeat-AAV blank group to investigate the effect of BDNF. Fear extinction in mice was evaluated by fear conditioning test (FC). The levels of BDNF and HDAC2 in mice hippocampus were detected by Western blot (WB). The expression of BDNF-overexpressing virus in hippocampus of mice was detected by immunofluorescence assay. Results (1) Compared with control group,fear extinction in the social defeat group was significantly decreased (P<0. 05). Compared with control group, the level of HDAC2(0. 50±0. 02) in the social defeat group was significantly increased (P<0. 001),while the level of BDNF(0. 16 ± 0. 03) was significantly decreased (P<0. 001) in the social defeat group. ( 2) After using SAHA,fear extinction of mice significantly improved (P<0. 05). Compared with control group,the level of HDAC2 (0. 26±0. 02) in the control-SAHA group was significantly decreased(P<0. 001),and the level of BDNF (0. 40±0. 03) was significantly increased (P<0. 001). Compared with social defeat group,the level of HDAC2 (0. 39±0. 03) in the social defeat-SAHA group was significantly decreased (P<0. 001),and the lev-el of BDNF (0. 28±0. 01) was significantly increased (P<0. 001). (3)After injection BDNF-overexpressing virus,fear extinction was significantly improved(P<0. 05). Conclusion SAHA can enhance fear extinction in mice with chronic social defeat stress and its mechanism may be related to the up-regulation of BDNF ex-pression in hippocampus by inhibiting HDAC2 in hippocampal.

20.
Article in Chinese | WPRIM | ID: wpr-755609

ABSTRACT

Objective To evaluate the effect of amitriptyline on the phosphorylation of histone deacetylase 5 (HDAC5) in the basolateral amygdala (BLA) of rats with neuropathic pain.Methods Thirty healthy male Wistar rats,weighing 250-300 g,were divided into 3 groups (n=10 each) using a random number table method:sham operation group (S group),neuropathic pain group (NP group) and amitriptyline group (A group).Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized rats.Amitriptyline 10 mg/kg was intraperitoneally injected every day on 14-35 days after establishing the model in group A,while the equal volume of normal saline was given instead of amitriptyline in S and NP groups.The mechanical paw withdrawal threshold (MWT) was measured on 3,7,14,21,28 and 35 days after establishing the model in each group.The forced swimming test was performed on day 36 after establishing the model,and immobility time,climbing time and swimming time were recorded.The rats were then sacrificed,and brain tissues in BLA were obtained for determination of the expression of HDAC5 and phosphorylated HDAC5 (p-HDAC5) (by Western blot) and expressionof HDAC5 mRNA (by real-time quantitative polymerase chain reaction).Results Compared with group S,the MWT was significantly decreased at each time point,the immobility time was prolonged,and the swimming time and climbing time were shortened in group NP,and the MWT was significantly decreased on days 14,21 and 28 after establishing the model,the expression of p-HDAC5 was down-regulated,and the expression of HDAC5 mRNA was up-regulated in group A (P<0.05).Compared with group NP,the MWT was significantly increased on days 21,28 and 35 after establishing the model,the immobility time was shortened,the climbing time was prolonged,the expression of p-HDAC5 was up-regulated,and the expression of HDAC5 mRNA was down-regulated in group A (P<0.05or 0.01).Conclusion The mechanism by which amitriptyline improves depression is associated with promoting the phosphorylation of HDAC5 in BLA of rats with NP.

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