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Diabetic kidney disease （DKD） is one of the most common microvascular complications in patients with diabetes. DKD is also the main cause of end-stage renal failure， with very complex pathogenesis. A large number of experiments have confirmed that epigenetic mechanisms， including histone chemical modifications and lipid metabolites 12/15-lipoxygenase （12/15-LO）， are involved in regulating the characteristic pathophysiological process of DKD， based on which， this review further explores the pathogenesis of DKD and provides the new research direction for DKD treatment.
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The abnormal lipids metabolism is a critical pathological feature of coronary heart disease (CHD). Additional supplemental intake of polyunsaturated fatty acid (PUFA) has long been considered to be an effective strategy for preventing CHD, but more and more clinical trials have denied this view. Still, it is ambiguity for the specific mechanism of PUFA in CHD. The experimental programs are compliant with ethical principles for animal use and have been approved by the Animal Experiment Ethics Committee of Jinan University. In the present study, we established an animal model by intake of omega-6 PUFA combined acute myocardial ischemia to explore the mechanism of CHD. Intragastric administration of linoleic acid (LA) for 14 days, intraperitoneal injection of isoprenaline (ISO) was applied to induce acute myocardial ischemia for the animal model establishment. The animal ultrasound imaging system was used to detect cardiac function in vivo after ISO injection for 24 h. Serum and heart tissue samples were collected for the myocardial enzyme, phospholipidomics analysis and molecular biological detection. Compared to the LA group, the cardiac function showed that the left ventricular ejection fraction (EF%) and the left ventricular shortening fraction (FS%) decreased, aspaetate aminotransferase (AST), creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH) increased in the LA + ISO mice. Compared to the ISO group, the phospholipidomics analysis showed that the PUFAs significantly were raised in the LA + ISO myocardium, and the content of oxidized phosphatidylethanolamine (ox-PE) changed most remarkable. Compared with the ISO group, the molecular biology detection showed that glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were depleted, the end-products of ox-PE were increased, and the level of arachidonic acid 12/15-lipoxygenase (ALOX15) protein expression increased obviously. We suggest that ALOX15 mediated phospholipid peroxidation might be the critical mechanism of LA increased the susceptibility of myocardial ischemia injury. This study provides an experimental basis for whether PUFA could be used as an alternative treatment strategy for CHD prevention and provides a new intervention target for the early prevention strategy of CHD.
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Ulomoides dermestoides es usado en medicina tradicional oriental para aliviar enfermedades inflamatorias y como afrodisíaco. En Colombia, comunidades campesinas lo consumen para el tratamiento del asma. El propósito de este estudio fue obtener extractos acuosos del cuerpo entero de U. dermestoides y explorar su potencial para inhibir enzimas involucradas en la biosíntesis de reguladores de la inflamación, la 15-lipoxigenasa (15-LOX) y las ciclooxigenasas COX-1 y COX-2 (COXs). Los extractos se obtuvieron con tampón salino fosfato 0,01M (PBS) y bicarbonato de amonio 0,1M (NH4HCO3), en presencia de un detergente (Tween-20 o Dodecilsulfato sódico, SDS). Posteriormente se determinó el contenido de proteínas totales solubles, el perfil electroforético y las actividades enzimáticas a 19 hidrolasas. Las inhibiciones 15-LOX y COXs se midieron por método colorimétrico y por inmunoensayo enzimático, respectivamente. El rendimiento más alto de proteínas se obtuvo con el tampón PBS/SDS (1,603 %p/p). Este extracto mostró 13 bandas electroforéticas mayoritarias, con tamaños entre 8,8 y 151,2 kDa; también, se demostraron actividades enzimáticafosfosfohidrolasas, peptidasas, esterasas, B-glucoronidasa, a-glucosidasa, N-acetil-B-glucosaminidasa y a-manosidasa. Todos los extractos mostraron actividad inhibitoria dual 15-LOX y COXs. Las inhibiciones 15-LOX y COX-1 más altas se obtuvieron con el extracto obtenido con PBS/SDS (15-LOX: 62,8±2,0%; COX-1: 88,5±3,9%). Adicionalmente, un análisis de regresión lineal simple mostró que no hay asociación entre la concentración de proteínas y la inhibición 15-LOX (valor p = 0,493), este resultado sugiere que la actividad anti-lipooxigenasa podría ser debido a compuestos no proteicos.
Ulomoides dermestoides is used in traditional oriental medicine to alleviate inflammatory diseases and as an aphrodisiac. In Colombia, rural communities consume it as treatment for asthma. The purpose of this study was to obtain aqueous extracts of whole body of U. dermestoides and explore their potential to inhibit enzymes involved in the biosynthesis of inflammation regulators, 15-lipoxygenase (15-LOX) and cyclooxygenases COX-1 and COX-2 (COXs). Extracts were obtained with phosphate buffered saline 0.01M (PBS) and ammonium bicarbonate 0.1M (NH4HCO3) in the presence of one detergent (Tween-20 or Sodium dodecyl sulfate, SDS). Then, total soluble protein, electrophoretic profile and enzymatic activities at 19 hydrolases were determined. Inhibition of 15-LOX and COXs were measured by colorimetric method and enzymatic immunoassay respectively. The highest protein yield was obtained with PBS/SDS buffer (1.603 %p/p). This extract showed 13 major electrophoretic bands with molecular weights between 8.8 and 151.2 kDa; also, enzymatic phosphohydrolase, peptidase, esterase, B-glucuronidase, a-glucosidase, N-acetyl-B-glucosaminidase and a-mannosidase activities were proven. All extracts showed dual inhibitory activity for 15-LOX and COXs. The higher inhibitions for 15-LOX and COX-1 were obtained with PBS/SDS extract (15-LOX: 62.8±2%; COX-1: 88.5±3.9%). Additionally, a simple linear regression analysis showed non-relationship between the protein concentration and 15-LOX inhibition (p value = 0.493). This result suggests that anti-lipoxygenase activity could be due to non-protein compounds.
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[ ABSTRACT] Tyrosine kinase inhibitors ( TKIs) are now advocated as the first-line treatment for chronic myeloid leukemia ( CML) , but facing resistance and relapse .Leukemia stem cells ( LSCs ) are leukemia-initiating cells as the source of resistance and relapse .It is therefore important to discover the molecular biomarker of LSCs for developing anti -LSC strategies in leukemic therapy .15-Lipoxygenase (15-LO) is a key enzyme in the pathway of arachidonic acid and plays an important role in the occurrence and development of CML , which is specifically required for chronic myeloid LSCs . This review summarizes the influence of 15-LO on the chronic myeloid LSC characteristics of marked survival , self-renewal, proliferation , differentiation and apoptosis .
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Objective To investigate the correlation between arachidonate 15-lipoxygenase (ALOX15)gene polymorphism and its genetic predisposition to coronary heart disease (CHD)in Han population of Shaanxi Province so as to provide the basis for early diagnosis and prophylaxis of CHD.Methods The single nucleotide polymorphisms (SNPs)of ALOX15’s rs916055,rs2619112,and rs2664593 were measured by using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)method in 105 CHD patients (CHD group)and 75 non-CHD patients (control group)who were matched in age and sex.Results The frequencies of genotypes and alleles of SNPs rs916055A/G in CHD group were significantly different from those in control group (P=0.000 1,P=0.000 1).The frequencies of genotypes and alleles of SNP rs2619112A/G in CHD group did not significantly differ from those in control group (P=0.134 2,P=0.143 8).The frequencies of genotypes of SNP rs2664593C/G in CHD group significantly differed from those in control group (P=0.002 7),but the frequencies of alleles were not significantly different (P=0.537 1).Logistic regression analysis indicated that the A allele of SNP rs916055 was an independent risk factor for CHD.Conclusion SNP rs916055 may be related to CHD and its A allele may be the genetic susceptibility gene for CHD.
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Objective:To evaluate the 15-lipoxygenase inhibitory activity of the methanol leaf extracts of Commelina benghalensis, Tradescantia fluminensis (T. fluminensis) and Tradescantia zebrina. Method: The inhibitory activity was evaluated using a spectrophotometric assay by observing the increase in absorbance at 234 nm due to the formation of the product 13-hydroperoxyoctadecadienoic acid. The extracts were also tested for the presence of terpenoids, saponins, tannins, flavonoids, steroids, phenolic compounds, alkaloids and cardiac glycosides. Results:All the extracts inhibited the action of 15-lipoxygenase at a concentration of 0.2 μg/mL. T. fluminensis and Tradescantia zebrina exhibited higher than 50%inhibition with T. fluminensis at 87.2%. T. fluminensis was partitioned with ethyl acetate and hexane and their IC50 values were determined at 8.72 μg/mL and 98.04 μg/mL, respectively. Conclusions:T. fluminensis is a potentially good source of 15-lipoxygenase inhibitors.
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<p><b>OBJECTIVE</b>To evaluate the 15-lipoxygenase inhibitory activity of the methanol leaf extracts of Commelina benghalensis, Tradescantia fluminensis (T. fluminensis) and Tradescantia zebrina.</p><p><b>METHOD</b>The inhibitory activity was evaluated using a spectrophotometric assay by observing the increase in absorbance at 234 nm due to the formation of the product 13-hydroperoxyoctadecadienoic acid. The extracts were also tested for the presence of terpenoids, saponins, tannins, flavonoids, steroids, phenolic compounds, alkaloids and cardiac glycosides.</p><p><b>RESULTS</b>All the extracts inhibited the action of 15-lipoxygenase at a concentration of 0.2 µg/mL. T. fluminensis and Tradescantia zebrina exhibited higher than 50% inhibition with T. fluminensis at 87.2%. T. fluminensis was partitioned with ethyl acetate and hexane and their IC50 values were determined at 8.72 µg/mL and 98.04 µg/mL, respectively.</p><p><b>CONCLUSIONS</b>T. fluminensis is a potentially good source of 15-lipoxygenase inhibitors.</p>
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BACKGROUND AND OBJECTIVES: In oral cavity cancer (OCC) cells, the effects of interleukin-4 (IL-4) are various according to the cell specificity. However, if IL-4 induces apoptosis on OCC cells, the mediator of this apoptosis is uncertain. Therefore, we investigated whether apoptosis of OCC cells occurs by IL-4 and whether 15-lipoxygenase-1 (15-LO-1) induced by IL-4 is the possible mediator of this apoptosis. MATERIALS AND METHODS: SCC 1483 cells were used. Flow cytometry and poly ADP-ribose polymerase cleavage were used to examine apoptosis. Western blot analysis and reverse transcription-polymerase chain reaction were used to measure 15-LO-1 protein and mRNA. RESULTS: The inhibition of cell proliferation by more than 50% was noted from 10 ng/ml of IL-4. At this dose, apoptosis was observed and this apoptosis was inhibited by 2.2 microM caffeic acid. 15-LO-1 expression was observed from the 8 hour treatment of IL-4 and apoptosis increased after the 24 hour treatment of IL-4. In this apoptosis, caspase cascade, cyclooxygenase-2, and non-steroidal anti-inflammatory drugs-activated gene-1 (NAG-1) were not involved. CONCLUSION: IL-4 induced apoptosis in SCC 1483 OCC cells and 15-LO-1 induced by IL-4 may mediate this apoptotic pathway.
Subject(s)
Adenosine Diphosphate Ribose , Apoptosis , Arachidonate 15-Lipoxygenase , Blotting, Western , Cell Proliferation , Cyclooxygenase 2 , Flow Cytometry , Interleukin-4 , Mouth Neoplasms , Mouth , RNA, Messenger , Sensitivity and SpecificityABSTRACT
BACKGROUND AND OBJECTIVES: 15-lipoxygenase-1 (15-LO-1) is involved in the differentiation of human tracheobronchial epithelial cells. Here we investigated the relation between 15-LO-1 expression and the differentiation of normal human nasal epithelial (NHNE) cells. MATERIALS AND METHODS: NHNE cells, RT-PCR, Western blot analysis, and scanning electron microscopy (SEM) were used. RESULTS: In retinoic acid (RA)-sufficient culture media, 15-LO-1 expression in NHNE cells increased time-dependently, but its expression was undetectable in RA-deficient culture media. Moreover, in RA-deficient culture media, IL-4 time-dependently induced 15-LO-1 expression at a concentration of 1 ng/mL. In addition, MUC8 gene expression, a marker of mucociliary differentiation, was up-regulated by 15-LO-1, which was itself induced by IL-4. In SEM, the ciliated epithelium was observed with the treatment of IL-4. CONCLUSION: Our findings suggest that 15-LO-1 may be related to the differentiation of human nasal epithelium, and that it may mediate the mucociliary differentiation of NHNE cells.
Subject(s)
Humans , Blotting, Western , Cell Differentiation , Cilia , Culture Media , Epithelial Cells , Epithelium , Gene Expression , Interleukin-4 , Microscopy, Electron, Scanning , Nasal Mucosa , TretinoinABSTRACT
BACKGROUND AND OBJECTIVES: The purpose of our study was to examine the expression of 15-lipoxygenase (15-LO) in human nasal mucosa and to investigate the change of expression of 15-LO and cyclooxygenase-2 (COX-2) as a function of mucociliary and squamous differentiation. MATERIALS AND METHOD: Human inferior turbinates were used and immunohistochemistry with 15-LO and COX-2 antibody was done. Passage-2 normal human nasal epithelial cell culture using air-liquid interface method was performed for 14 days and the cells were divided as retinoic acid (RA)-sufficient and RA-deficient group. Western blot analysis for 15-LO and COX-2 expression was performed on each group on 0, 7, and 14 days. RESULTS: 15-LO expression of mucociliated epithelium was noted in ciliated cells and basal cells, but was not found in goblet cells and secretory acini. In squamous epithelium, the expression of 15-LO was weaker than that in the mucociliated epithelium, but the expression of COX-2 showed no difference between them. In Western blot analysis, 15-LO expression was significantly higher in RA-sufficient culture than in RA-deficient culture and this expression was time-dependent. COX-2 expression was almost same level in RA-deficient culture, but its expression was significantly higher in RA-sufficient culture on 7 and 14 days than on zero day. CONCLUSION: 15-LO and COX-2 may be related to differentiation and development of nasal epithelial cells. However, it is unclear whether this relationship is direct or indirect effect of 15-LO and COX-2. This question remains to be solved.
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HumansABSTRACT
Hypoxic pulmonary hypertension(HPH) is a common disease featured by acute hypoxic pulmonary vasoconstriction(HPV) and chronic hypoxic pulmonary vascular remolding(HPVR) leading to the sustained increasing of pulmonary artery pressure.There are many mediators involved in the HPH but none can illustrate it successfully.Primary work has found 15-lipoxygenase(15-LO) and its catalyzed production 15-hydroxyeicosatetraenoic acid(15-HETE)(from arachidonic acid) are up-regulated in pulmonary vascular when exprosed to hypoxia.And it has been found 15-LO/15-HETE involved in many processes of both the HPV and HPVR,indicating 15-LO/15-HETE may be an important mediator of HPH.Advances research on 15-LO/15-HETE may illustrate the mechanism of HPH,and will give some message in looking for a potential clinical target of HPH.
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Aim The purpose of this study was to compare the differential expression of 15-lipoxygenase isoenzymes in the pulmonary arteries between normoxia and hypoxia and to explore their roles in the formation of hypoxic pulmomary vasoconstriction. Method Eighteen SD rats were randomly divided into two groups(n=9):the normoxic control group breathing fresh gas and the hypoxic group breeding in animal hypoxic incubator.Immunohistochemical method,in situ hybridization and Western blot were employed to determine certain 15-lipoxygenase isoenzymes which involved in the process of hypoxic pulmonary vasoconstriction.Results ①In normoxic control group,the expression of 15-LO-1 protein was detected in the pulmonary arteries;but the expression of 15-LO-2 protein wasn’t detected.②The expression of 15-LO-1 protein in hypoxic group was much stronger than that in normoxic group (P