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Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.
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Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.
Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.
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Animals , Male , Rats , Thioredoxins/metabolism , Ventricular Remodeling , Vitamin D , Rats, Wistar , Oxidative Stress , Cell Cycle Proteins , Dietary SupplementsABSTRACT
Thioredoxin is one of important disulfide bond reductases in cells ,which plays important role in antioxi‐dant stress of cells and maintaining reduced state of intracellular protein and its normal functioning .The present ar‐ticle set forth the possible biological function of thioredoxin in atherosclerosis from its antioxidation ,anti－apopto‐sis ,anti－inflammation and regulation of blood lipid and glucose metabolism etc .,aiming at providing new targets for prevention and treatment of atherosclerosis .
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Objective@#To observe the effects of recombinant adenovirus with human thioredoxin (hTRX) on the inflammatory response in mice with viral myocarditis and explore the related mechanism.@*Methods@#Sixty Balb/c male mice were randomly divided into control group, myocarditis group, and hTRX group according to the random number table (n=20 each group). The myocarditis group and hTRX group were injected with 100 TCID50 Coxackie virus B3 (0.1 ml) in the abdomen and control group were injected with saline. Two days before the viral injection, the hTRX group were injected with recombinant adenovirus vector coding the human thioredoxin gene by pericardial puncture and the control group and myocarditis group were injected with recombinant adenovirus vector without coding gene by pericardial puncture, all these mice were killed and hearts were removed 7 days later. The morphology of myocardial tissue in each group was detected by HE staining and the ultrastructure changes by electron microscope. The protein expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and NF-κB were detected by ELISA and Western blot. Immunohistochemical staining was performed to observe the protein expression levels of thioredoxin.@*Results@#Necrosis of myocardial cells and a small amount of cell infiltration were found in the myocarditis group and necrosis and cell infiltration were significantly reduced in the hTRX group and no myocardial lesion was found in control group on HE stained sections. Electron microscope examination evidenced cell swelling and dissolved myofilament, vacuoles degeneration in mitochondria in the myocarditis group. These changes were significantly reduced in the hTRX group. There was no myocardial lesion in control group. The protein expression of TNF-α, IL-1β and NF-κB were significantly upregulated in myocarditis group than in control group (all P<0.01). The protein expression of TNF-α, IL-1β and NF-κB were significantly downregulated in hTRX group than in myocarditis group (all P<0.01). Immunohistochemical staining showed that protein expression of hTRX was higher in hTRX group than in myocarditis group (P<0.01).@*Conclusion@#Recombinant adenovirus hTRX can attenuate cardiac injury in mice with acute myocarditis via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-1β and NF-κB.
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Objective To evaluate the role of thioredoxin?interacting protein(TXNIP)∕oligomer?ization domain?like receptor family pyrin domain?containing 3(NLRP3)signaling pathway in renal ische?mia?reperfusion(I∕R)injury in diabetic rats. Methods Pathogen?free healthy male Sprague?Dawley rats, aged 8-12 weeks, weighing 200-220 g, were used in the study. Diabetes mellitus was induced by intrap?eritoneal injection of 1% streptozotocin 65 mg∕kg and confirmed by blood glucose≥16.7 mmol∕L 3 days lat?er. Twenty?four diabetic rats were divided into 3 groups(n=8 each)using a random number table: sham operation group(group S), renal I∕R group(group I∕R)and resveratrol(TXNIP inhibitor)group (group R). Resveratrol 10 mg∕kg was intraperitoneally injected every day for 7 consecutive days starting from 3rd week after successful establishment of the model in group R. At 4th week after successful establish?ment of the model, renal I∕R was produced by occlusion of bilateral renal pedicles for 25 min followed by reperfusion in anesthetized rats in group R. The animals were sacrificed at 48 h of reperfusion, and renal specimens were obtained for microscopic examination of pathologic changes and for measurement of malondi?aldehyde(MDA)content, superoxide dismutase(SOD)activity and superoxide anion scavenging capa?bility(using colorimetric method), interleukin?1beta(IL?1β)and IL?18 contents(by enzyme?linked immunosorbent assay), cell apoptosis(using TUNEL)and expression of TXNIP, NLRP3 and caspase?1 in renal tissues(using Western blot). Blood samples were obtained from the left ventricle for determination of serum urea nitrogen(BUN)and creatinine(Cr)concentrations. Results Compared with group S, the serum Cr concentration and apoptosis index were significantly increased, superoxide anion scavenging capability in renal tissues was decreased, and the expression of TXNIP, NLRP3 and caspase?1 was up?reg?ulated in I∕R and R groups, and the serum BUN concentration and contents of MDA, IL?1β and IL?18 in renal tissues were increased, the SOD activity was decreased(P<0.05), and the pathological changes of renal tissues were aggravated in group I∕R. Compared with group I∕R, the serum BUN and Cr concentra?tions were significantly decreased, the contents of MDA, IL?1β and IL?18 and apoptosis index were de?creased, the SOD activity and superoxide anion scavenging capability were increased, the expression of TXNIP, NLRP3 and caspase?1 was down?regulated(P<0.05), and the pathological changes of renal tis?sues were significantly attenuated in group R. Conclusion The pathophysiological mechanism of renal I∕R injury is associated with the activation of TXNIP∕NLRP3 signaling pathway in diabetic rats.
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Objective:To establish a Mongolian gerbils model by long-term infection of Helicobacter py-lori (Hp) with highly-expressed thioredoxin-1 (Trx1 ) gene and to investigate the histopathological findings of gastric mucosa in Mongolian gerbils.Methods:In this study,75 healthy male Mongolian ger-bils were randomly divided into 3 groups:Hp with highly-expressed Trx1 gene group (n =30),Hp with lowly-expressed Trx1 gene group (n =30),and control group (n =15).The animals underwent gastric perfusion of Hp suspension once a week for 5 weeks.The animals were sacrificed at the end of 4,20, 34,48,70,and 90 weeks after inoculation for detecting Hp colonization by rapid urease test and War-thin-Starry silver staining and histological examination,respectively.Results:(1)The Mongolian gerbil model of long-term infection of Hp with highly-expressed Trx1 gene and lowly-expressed Trx1 gene were successfully established.(2)The macroscopic mucosal lesions,including erythema,uneven,erosion, nodules,etc.could be observed in experimental groups.The severity of lesions and the time when lesions occurred in Hp with highly-expressed Trx1 gene group were heavier/earlier than that in Hp with lowly-ex-pressed Trx1 gene group.(3)Histopathologically,the gastric mucosa of Hp with highly-expressed Trx1 gene group showed the mild dysplastic hyperplasia of epithelial cells 34 weeks after the Hp inoculation, and the time was in the 48th week in Hp with lowly-expressed Trx1 gene group.At the end of the 90th week after Hp inoculation,the gastric adenocarcinoma could be detected in the two experimental groups (71.4% vs.42.8%).The difference between the two experimental groups did not reach statistical sig-nificance (P =0.592),which might be due to the small sample capacity and /or short observation time. In addition,there were 2 cases with severe epithelial dysplastic hyperplasia in Hp with highly-expressed Trx1 gene group,and only 3 cases with moderate epithelial dysplastic hyperplasia in Hp with lowly-ex-pressed Trx1 gene group.The uninfected control animals showed no abnormal findings throughout the en-tire observation period.Conclusion:Hp with highly-expressed /lowly-expressed Trx1 gene colonizes stab-ly in the glandular gastric mucosa of Mongolian gerbils.The histological changes after infection are similar to those of the Hp infected human being,and Hp with highly-expressed Trx1 gene cause the injury of gas-tric mucosa and the occurrence of gastric adenocarcinoma.Trx1 maybe the virulence factor that partici-pates in the pathogenesis of gastric cancer and Hp expressing high levels of Trx1 should be highly toxic for gastric diseases in China.
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Introducción: La disfunción ventricular posisquémica (miocardio atontado) involucra un aumento del estrés oxidativo. En este sentido, la célula cuenta con mecanismos de defensa, como la tiorredoxina-1, un antioxidante que protege al miocardio de la lesión por isquemia/reperfusión, reduciendo el tamaño del infarto. Objetivo: Evaluar el comportamiento de la función ventricular sistólica y diastólica, particularmente estudiando la rigidez miocárdica y la relajación isovolúmica en el miocardio atontado en diferentes ratones transgénicos. Material y métodos: Se utilizaron corazones de ratones que sobreexpresan tiorredoxina-1 y de ratones transgénicos que sobreexpresan tiorredoxina-1 mutada en su sitio activo (dominante negativo), comparados con los de ratones no transgénicos, los cuales fueron sometidos a 15 minutos de isquemia global y 30 minutos de reperfusión utilizando la técnica de Langendorff. Se evaluó la función ventricular sistólica y diastólica y se calculó el t63 y el t93 como índice de relajación isovolúmica. Resultados: Las mediciones a los 30 minutos de reperfusión mostraron una mejoría significativa del estado contráctil en los ratones tiorredoxina-1 (57,4 ± 4,9 mm Hg; p ≤ 0,05 vs. no transgénicos) y también en la rigidez (11,8 ± 2,9 mm Hg; p ≤ 0,05 vs. no transgénicos). Por otra parte, en los ratones dominantes negativos se observó un aumento de la rigidez (37,7 ± 5,5 mm Hg; p ≤ 0,05 vs. no transgénicos) y un enlentecimiento de la relajación a los 30 minutos de la reperfusión (78,2 ± 9,8 mseg; p ≤ 0,05 vs. no transgénicos). Conclusión: Este trabajo evidencia el rol protector de la tiorredoxina-1 en el miocardio atontado y su importancia fisiopatológica en ratones que sobreexpresan este antioxidante.
Background: Postischemic ventricular dysfunction (myocardial stunning) involves increased oxidative stress. In this sense, the cell has defense mechanisms, as thioredoxin-1, an antioxidant that protects the myocardium from ischemia/reperfusion injury, reducing infarct size. Objective: The aim of this study was to evaluate systolic and diastolic ventricular function, specifically analyzing myocardial stiffness and isovolumic relaxation, during myocardial stunning in different transgenic mice. Methods: Hearts from mice overexpressing thioredoxin-1 and transgenic mice overexpressing thioredoxin-1 with gene mutation in its active site (dominant negative) were compared with hearts from non-transgenic mice after 15-minute global ischemia and 30-minute reperfusion using the Langendorff technique. Systolic and diastolic ventricular function was evaluated and t63 and t93 were calculated as ventricular relaxation index. Results: At 30-minute reperfusion, thioredoxin-1 mice showed a significantly improved contractile state (57.4±4.9 mmHg; p≤0.05 vs. non-transgenic mice) and stiffness (11.8±2.9 mmHg; p≤0.05 vs. non-transgenic mice). Conversely, at the same reperfusion time, dominant negative mice exhibited increased stiffness (37.7±5.5 mmHg; p≤0.05 vs. non-transgenic mice) and slower relaxation (78.2±9.8 ms; p≤0.05 vs. non-transgenic mice). Conclusion: This study reveals the protective role of thioredoxin-1 on myocardial stunning and its pathophysiological importance in mice overexpressing this antioxidant.
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[ Abstract] Ischemic brain injury is closely associated w ith oxidative stress, neuron loss, and inflammatory reaction. The thioredoxin system is an important antioxidant system in human body. It plays the important roles in the process of fighting against oxidative stress damage, inhibiting apoptosis and inflammation. In recent years, the roles of thioredoxin system in cerebral ischemia have attracted more and more attention. This article review s the roles of thioredoxin in cerebral ischemia.
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Objective To investigate the association of serum thioredoxin (Trx) and 3-nitrotyrosine (3 NT) levels with diabetic retinopathy (DR) in the elderly,in order to provide new evidence for clinical prevention and treatment of DR.Methods A total of 156 patients diagnosed with type 2 diabetes mellitus (T2DM) at the Department of Endocrinology were selected.Based on of fundus examination results,the patients were divided into the non-diabetic retinopathy group (NDR) (n=52),the nonproliferative diabetic retinopathy group (NPDR) (n =52) and the proliferative diabetic retinopathy group (PDR) (n=52),with 52 healthy people enrolled in the control group (CON).Solid phase enzyme linked immunosorbent assays (ELISA) were used to measure serum levels of Trx and 3-NT in all subjects.The results were statistically analyzed.Results The expression of Trx in the serum was the lowest in CON,followed by NDR,NPDR and PDR [[(324.1± 69.3) pg/L,(429.5±36.9) pg/L,(515.2±43.0) pg/L and (588.8±112.5) pg/L,respectively],and there were statistically significant differences between the groups (F=19.00,P=0.000).Similarly,the expression of 3 NT in the serum was the lowest in CON,followed by NDR,NPDR and PDR [(0.16±0.07) ng/L,(0.22±0.05) ng/L,(0.28±0.06) ng/L and (0.38±0.09) ng/L,respectively],and there were statistically significant differences between the groups (F=28.78,P=0.000).The expression levels of Trx and 3 NT in the serum were positively correlated with the severity of DR (r=0.64 and 0.66,respectively,P 0.001 for both).There was a correlation between serum Trx and 3-NT (r 0.71,P=0.001).Conclusions Serum levels of Trx and 3 NT are increased with the severity of DR,and they are positively correlated with the severity of DR.
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Thioredoxin-related protein 14 (TRP14),a new member of Trx family,is a novel disulfide reductase with conservative CPDC motif.Its structure and function are comparable to Trx,which is the representative member of Trx family.However,there are many differences.When tumor necrosis factor-α (TNF-α) induced cells to produce the active oxygen,TRP14 can change oxidatin state of dynein light chain(its substrate),act as a sensor of the intracellular redox state to regulate NF-κB signaling pathways induced by TNF-α,MAPK and apoptosis signaling pathways.
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Objective To evaluate the changes in the expression of small intestinal thioredoxin 2 (Trx2) during different periods after orthotopic liver autotransplantation (OLAT) in rats.Methods Forty Sprague-Dawley rats,aged 8-10 weeks,weighing 210-260 g,were randomly divided into 2 groups using a random number table:sham operation group (group S,n =8) and OLAT group (n =32).Intestinal tissues were removed at 4,8,16 and 24 h after OLAT for microscopic examination and for determination of the levels of superoxide anion (O2--),hydrogen peroxide (H2 O2),glutathione peroxidase (GSH-Px),reduced glutathione (GSH) and Trx2.Intestinal damage was assessed and scored according to Chiu.Results Compared with S group,the Chiu's score and O2--activity at 4,8 and 16 h after OLAT and H2O2 content at 4 and 8 h after OLAT were significantly increased,and the levels of GSH-Px and GSH and expression of Trx2 at 4 and 8 h after OLAT were decreased in OLAT group (P ＜ 0.05).Chiu' s score at 4,16 and 24 h after OLAT and H2O2 content at 16 and 24 h after OLAT were significantly lower than those at 8 h in OLAT group (P ＜ 0.05).Conclusion The rats undergo decreased antioxidant capacity in the early phase and recovery in the late phase mediated by small intestinal Trx2 after OLAT.
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Objective To investigate the molecular mechanisms of protective effects of thioredoxin (Trx) on human vascular endothelial cells in atherosclerosis.Methods The cell models of Trx-overexpressing cells (Ad Trx) and the control cells (Ad-con) were established by adenovirus vector gene transfer technology in human umbilical vein endothelial cells (HUVECs).The oxidized low density lipoprotein,a risk factor of atherosclerosis,was used as a stimulator.Western blot and indirect immunofluorescence were used to detect the protein expression levels and the cellular localization of Trx,adhesion molecules (ICAM-1,VCAM-1) and the upstream signal pathways.Trx activity was detected by insulin disulfide reduction assay,and cellular reactive oxygen species (ROS)production was detected by fluorescent probe DCFH-DA.Results As compared with control group,Trx protein expression level was enhanced in Ad-trx group and the Trx activity in Ad-Trx group was upregulated by (26.2 ±3.3)％.The result of ROS detection showed that overexpression of Trx significantly inhibited the cellular ROS generation.As compared with control group,overexpression of Trx obviously inhibited the adhesion molecules expression but markedly promoted the phosphorylation of Smad3 in endothelial cells with or without oxLDL stimulation (P＜0.05).Pretreatment of cells with SIS3,a specific inhibitor of Smad3 phosphorylation,reversed Trx-induced inhibition of adhesion molecules expression.Further studies showed that pretreatment of cells with SIS3 enhanced oxLDL-induced AP-1 subunit c-fos nuclear expression.Conclusions The enhancement of Smad3 phosphorylation and c-Fos nuclear expression are mainly responsible for the Trx-induced downregulation of adhesion molecules.
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Objective To investigate the variation of the thioredoxin system (Trx),and the role of it in transient out-ward potassium current (Ito) channels in left ventricular myocytes of diabetes mellitus (DM) in rats. Methods Forty-five SD rats were divided into DM group and control group. DM group were treated with streptozotocin (STZ) to induce DM model. The values of left ventricular end diastolic diameter (LVEDD), end-systolic diameter (LVESD), fractional shortening (LVFS), ejection fraction (LVEF) and heart rate (HR), QRS duration and corrected QT (QTc) interval were detected by echocardiogra-phy (UCG) and electrocardiogram (ECG) in two groups. The left ventricular myocardial tissue samples were taken to detect the Trx,glutaredoxin (GRX),thioredoxin reductase (TrxR) and glutathione reductase (GR) by using UV spectrophotometer. The level of free thiol (P-SH) of total cardiac protein was detected by 5, 5′-dithio-bis-2-nitrobenzoic acid method. Ito of the cardiomyocytes was recorded by whole-cell patch-clamp method. After being incubated in vitro with insulin(Ins), treated with TrxR inhibitor-auranofin(AF) and 13-cis-retinoic acid(RA), the changes of Ito of the cardiomyocytes were observed. Results Compared with control group, the values of heart rate (HR), left ventricular minor axis decurtaion rate (LVFS), left ventricular ejection fraction (LVEF) and TrxR were lower in DM group. The values of LVEDD, LVESD, QRS and QTc inter-vals, Trx, Grx and P-SH were higher in DM group than those of control group. Ito density was significantly higher in DM+Ins group than that of DM group, Ins+RA group and Ins+AF group when the stimulation voltage ≥ 0 mV (P ＜ 0.05). Conclusion The impaired Trx system in diabetic rat myocardium was the electrophysiological basis of the reduced ventric-ular function and arrhythmia. And Ins was able to reverse the decreased Ito of cardiomyocytes in DM rats.
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Thioredoxin (Trx) is a class of small redox proteins which is widely found in all organisms.It acts as antioxidant by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange.Recently,thioredoxin is found to be over-expressed in many kinds of tumor,which is closely associated with tumor cell proliferation,apoptosis and cell cycle control.Trx is also found to promote the synthesis and stabilization of the HIF-1α protein.It is also related to the control of reactive oxygen species and chemoresistance of tumor cells.Trx has been proved to play an important role in promoting the metastasis of cancer,and may become a potential target for anti-metastasis of cancer.
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Thioredoxin-1 (Trx-1) is one of important anti-oxidative molecules to overcome the oxidative stress. The aim of the present study is to investigate the clinical relationship between serum concentration of Trx-1 on the pre-percutaneous coronary intervention (prePCI) and myocardial damage amount in the patients with acute myocardial infarction with the culprit lesion in only the left anterior descending artery on coronary angiography (n = 100). Initial value of creatine kinase (CK) was 368.3 +/- 531.4 U/L, and MB isoenzyme of CK (CK-MB) level was 22.92 +/- 33.8 ng/mL, and cardiac specific troponin T (cTnT) level was 0.61 +/- 1.6 ng/mL. Positive correlations were observed between prePCI Trx-1 level and initial CK (P = 0.005, r = 0.281), and cTnT (P < 0.001, r = 0.453), peak CK (P = 0.001, r = 0.316) in all patients, but the statistical relation was observed only in ST segment elevation myocardial infarction (STEMI) patients (P = 0.008, r = 0.329 for initial CK, P = 0.001, r = 0.498 for initial cTnT, P = 0.005, r = 0.349 for peak CK), not in Non-STEMI patients. Conclusively, we consider prePCI serum Trx-1 as a predictor for myocardial damage amount in patients with STEMI.
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Adult , Aged , Female , Humans , Male , Middle Aged , Acute Disease , Biomarkers/blood , Coronary Angiography , Creatine Kinase/blood , Creatine Kinase, MB Form/blood , Echocardiography , Myocardial Infarction/blood , Myocardium/pathology , Percutaneous Coronary Intervention , Thioredoxins/blood , Troponin T/bloodABSTRACT
Objective To explore the effects of expression of thioredoxin-2(Trx-2) suppressed by small interference RNA(SiRNA) in A549 cells exposed to hyperoxia on expression of nicotinamide adenine dinucleotide(NADH) dehydrogenase subunit 1(ND1)and cytochrome C oxidase Ⅰ(COX Ⅰ). Methods A549 cells were gained by serial subcultivation in vitro and transfered with synthetic Trx-2 sequence-specific SiRNA and then were randomly divided into air group without interference,hyperoxia group without interference,air group after interference,and hyperoxia group after interference.After exposure to oxygen or room air for 12,24 and 48 h,expressions of Trx-2,ND1 and COX Ⅰ mRNA of these cells were detected by reverse transcription-polymerase chain reaction (RT-PCR),and Trx-2 protein was detected by Western blot. Results (1)Sequence-specific SiRNAtargeting Trx-2 could significantly down-regulate its expression in A549 cells.(2)Trx-2 mRNA levds inhyperoxia group without interference at 24 h was higher than those in air group without interference(0.7799±0.1249 VS 0.4424±Ⅰ.1140,P<0.05).Th-2 mRNA levels in hyperoxia group after ireedcrence at 24 hand 48 h were 0.2774±0.0174 and 0.2587±0.0069,lower than those in air group after interference andhyperoxia group without interference (P<0.05).(3)ND1 mRNA levels in hyperoxia group without interference at 24 h was 0.6609±0.0368,lower than those in air group without interference(0.8898±0.1049)(P<0.05).ND1 mRNA levels in hyperoxia group after interference at 12 h was 0.8848±0.0135,higher than those in air group after imederence(P<0.05).ND1 mRNA levels in hypemxia group afterinterference at 48 h was 0.3808±0.0937,lower than those in air group after imerference and hyperoxiagroup without interference(P<0.05).(4)COXI mRNA levels in hypemxia group without inteference at 12,24 and 48 h were 1.7313±0.4331,2.1929±0.6722 and 2.0754±0.2584,higher than those in air group witheUt interference,respectively (P<0.05). Conclusions ND1 and COXⅠ participate in thedevelopment of hyperoxia indUCed lung.injury,and Trx-2 is likely to have protective effect on mitochondria ofA549 cells in hyperoxia lung injury.
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Objective To investigate the changes and potential roles of the expression of apoptosis signal-regulating kinase 1(ASK1),thioredoxin(Trx)and thioredoxin reductase(TrxR)in the pathogenesis of lung injury of premature newborn rats exposed to hyperoxia. Methods In the first day after delivery,preterm SD rats were randomly divided into air group and hyperoxia group with 64 rats in each.The rats were respectively sacrificed at 1,4,7,10 and 14 days after air or hyperoxia exposure.Sections of 1ungs were stained with HE to observe the histologic changes.Trx and TrxR mRNA were detected by reverse transcription-polymerase chain reaction(RT-PCR).Immunohistochemistry was used to detect the expression and distribution of ASK1.Western blot was used to detect the expression of ASK1 protein. Results Rats in hyperoxia group showed typical lung injury,which was characterized by alveolitis and delayed of lung development.Immunohistochemistry detected that ASK1 expressed generally in the cytoplasm of both alveolar epithelial cells and vascular endothelial cells:ASK1 protein expression in hyperoxia group at 1th and 4th day were 0.4382±0.0227 and 0.5270±0.0432,higher than in the air group(0.3458±0.0263 and 0.3760±0.0058)(P<0.01),and it was until 7th day that the expression became weaker(0.4343±0.0254),but still higher compared with the air group(0.3473±0.0220)(P<0.01).Compared with the air group,Trx and TrxR mRNA of the hyperoxia group increased significantly and peaked at lOth day(0.6860±0.0811)and 7th day(2.0351±0.1600),respectively(P<0.05).ASK1 protein expressions resulting
ABSTRACT
BACKGROUND AND OBJECTIVES: The thioredoxin (TRx) system is a ubiquitous thiol oxidoreductase pathway that regulates cellular reduction/oxidation status. Although endothelial cell (EC) hypoxic damage is one of the important pathophysiologic mechanisms of ischemic heart disease, its relationship to the temporal expression pattern of the TRx system has not yet been elucidated well. The work presented here was performed to define the expression pattern of the TRx system and its correlation with cellular apoptosis in EC lines in hypoxic stress. These results should provide basic clues for applying aspects of the TRx system as a therapeutic molecule in cardiovascular diseases. SUBJECTS AND METHODS: Hypoxia was induced with 1% O2, generated in a BBL GasPak Pouch (Becton Dickinson, Franklin Lakes, NJ, USA) in human endothelial progenitor cells (hEPC) and human umbilical vein endothelial cells (HUVEC). Apoptosis of these cells was confirmed by Annexin-V: Phycoerythrin flow cytometry. Expression patterns of TRx; TRx reductase; TRx interacting protein; and survival signals, such as Bcl-2 and Bax, in ECs under hypoxia were checked. RESULTS: Apoptosis was evident after hypoxia in the two cell types. Higher TRx expression was observed at 12 hours after hypoxia in hEPCs and 12, 36, 72 hours of hypoxia in HUVECs. The expression patterns of the TRx system components showed correlation with EC apoptosis and cell survival markers. CONCLUSION: Hypoxia induced significant apoptosis and its related active changes of the TRx system were evident in human EC lines. If the cellular impact of TRx expression pattern in various cardiovascular tissues under hypoxia or oxidative stress was studied meticulously, the TRx system could be applied as a new therapeutic target in cardiovascular diseases, such as ischemic heart disease or atherosclerosis.