Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet β cells

The Journal of Biological Chemistry
Abass M ContehAmelia K Linnemann

Abstract

In type 1 diabetes, an autoimmune event increases oxidative stress in islet β cells, giving rise to cellular dysfunction and apoptosis. Lipoxygenases are enzymes that catalyze the oxygenation of polyunsaturated fatty acids that can form lipid metabolites involved in several biological functions, including oxidative stress. 12-Lipoxygenase and 12/15-lipoxygenase are related but distinct enzymes that are expressed in pancreatic islets, but their relative contributions to oxidative stress in these regions are still being elucidated. In this study, we used mice with global genetic deletion of the genes encoding 12-lipoxygenase (arachidonate 12-lipoxygenase, 12S type [Alox12]) or 12/15-lipoxygenase (Alox15) to compare the influence of each gene deletion on β cell function and survival in response to the β cell toxin streptozotocin. Alox12-/- mice exhibited greater impairment in glucose tolerance following streptozotocin exposure than WT mice, whereas Alox15-/- mice were protected against dysglycemia. These changes were accompanied by evidence of islet oxidative stress in Alox12-/- mice and reduced oxidative stress in Alox15-/- mice, consistent with alterations in the expression of the antioxidant response enzymes in islets from thes...Continue Reading

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Citations

Sep 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marimar Hernandez-PerezRyan M Anderson
Apr 26, 2020·European Journal of Pharmacology·Changqing DongQiaoyan Guo
Jun 17, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhonghua ZhengShiwei Duan
May 1, 2021·Life·Valentina BrilloRoberto Costa
May 18, 2021·Free Radical Biology & Medicine·Julia Bahja, Marcus K Dymond
Jun 3, 2021·Biomolecules·Abhishek KulkarniIsabel Casimiro

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