15-LOX Expression Research Articles

The effect of eight weeks of high-intensity interval training and moderate-intensity continuous training on some factors causing oxidative stress in the cardiomyocytes of mice with type II diabetes

Background and aims: Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality among diabetic patients. This study aimed to compare and investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on oxidative stress as one of the key links in the development of DCM in mice with type 2 diabetes mellitus (T2DM). Methods: Forty male C57BL/6J mice were randomly assigned to four groups of equal number (Control, T2DM, T2DM+HIIT, and T2DM+MICT). After the induction of T2DM, HIIT and MICT programs were conducted 5 days a week for 8 weeks. At the end of the experimental period, blood and heart samples were collected for subsequent measurements. Results: T2DM significantly up-regulated the levels of advanced glycation end products (AGEs, P=0.001) and the expression of 15-lipoxygenase (15-LOX, P=0.001) and 4-hydroxy-2-nonenal (4-HNE, P=0.001) compared to controlled mice. After 8 weeks of training, HIIT and MICT programs increased the levels of insulin (P<0.001) while reducing the levels of fasting blood glucose (P<0.001, P=0.024, respectively). On the other hand, it was found that HIIT and MICT programs significantly decreased the levels of AGEs (P<0.001), expression of 15-LOX (P=0.006, P=0.019, respectively), and 4-HNE (P=0.008 and P=0.035, respectively). Conclusion: Our findings revealed that exercise training, particularly MICT, will be highly helpful in the prevention of DCM through the improvement of glucose metabolism and reduction of 15-LOX expression.

The role of macrophages phenotypes in the activation of resolution pathways within human granulosa cells

BackgroundInflammatory state within the ovaries can disrupt normal follicular dynamics, leading to reduced oocyte quality and infertility. How the production of inflammatory mediators generated by macrophages with different gene expression profile (M1 and M2) might activate inflammatory pathways, such as cyclooxygenase-2 (COX-2) and 5-, 12-, and 15-lipoxygenase (LOX), in human granulosa cells (hGCs) remains unclear.MethodsIn this study, we evaluated how M1 and M2 macrophages found in the ovaries affect the functions of hGCs isolated from women undergoing assisted reproductive technology (ART) and human ovarian granulosa COV434 cells. For this purpose, a model of interaction between hGCs and COV434 cells and conditioned media (CMs) obtained from culture of M0, M1 and M2 macrophages was established. We used real-time PCR and western blotting to detect the expression of COX-2 and 5-, 12-, and 15-LOX as biomarkers of oocyte competence.ResultsOur data showed that M2 macrophages with anti-inflammatory characteristics were able to significantly increase the expression of COX-2 in hGCs. We also demonstrated that M1 macrophages with pro-inflammatory characteristics were able to significantly increase the expression of 12-LOX in hGCs. However, there was no observed expression of 5-LOX and no significant alteration in the expression of 15-LOX in hGCs. Regarding COV434 cells, we found that CM from M2 macrophage resulted in an increase in COX-2, 5-LOX and 15-LOX mRNA and protein levels. No expression of 12-LOX by COV434 cells was observed when exposed to CMs from M1 and M2 macrophages.ConclusionsOur research indicated that the production of pro-resolving mediators by hGCs can, at least in part, reverse the physiological inflammation present in the ovaries.

Abstract P119: The 15-lipoxygenase-derived Oxylipins 15-HETrE And 15-HETE Inhibit Platelet Activation In Part Through Activation Of PPARs

Cardiovascular disease is the leading cause of mortality in the US annually. The underlying cause of mortality in cardiovascular disease is the formation of platelet-rich clots that occlude blood vessels due to aberrant platelet activation. While antiplatelet therapeutic intervention has significantly reduced the risk of an occlusive thrombotic event, many patients remain at risk for a myocardial infarction or stroke. The antiplatelet and antithrombotic effects of omega-6 polyunsaturated fatty acids are primarily attributed to its metabolism to bioactive metabolites by oxygenases such as lipoxygenases (LOX). LOXs are a group of lipid-peroxidizing enzymes named according to the specific position where they add an oxygen to arachidonic acid: 5-LOX, 12-LOX, and 15-LOX. Previous studies from our group have demonstrated that dihomo-γ-linolenic acid and arachidonic acid regulate platelet function through their respective 12-LOX-derived oxylipins, 12(S)-hydroxyeicosatrienoic (12-HETrE) and 12(S)-hydroxyeicosatetraenoic acid (12-HETE). While the expression of 15-LOX in platelets is controversial, platelets have demonstrated the ability to generate the 15-LOX-derived bioactive metabolites. In this study we sought to elucidate the mechanistic effects of 15(S)-hydroxyeicosatrienoic acid (15-HETrE) and 15(S)-hydroxyeicosatetraenoic (15-HETE) on platelet reactivity. Washed human platelets were treated with 15-HETrE or 15-HETE and platelet aggregation, integrin αIIbβ3 activation, calcium mobilization, and granule secretion were quantified. Both 15-HETrE and 15-HETE were shown to inhibit platelet aggregation mediated by collagen. In comparison to vehicle-treated platelets, treatment with 15-HETrE or 15-HETE inhibited agonist-induced intracellular signalling events, including PKC activation, calcium mobilization, and granule secretion. Surprisingly, while 15-HETrE was shown to inhibit platelets through a signalling cascade involving the activation of PPARβ, 15-HETE’s inhibitory effect was shown to involve the activation of PPARα and the inhibition of 12-HETE production. A better understanding of the effects of 15-LOX oxylipins in platelets could lead to the identification of novel antiplatelet therapies.