Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet {beta} cells [Signal Transduction]

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 these mice. Additionally, islets from Alox12−/− mice displayed a compensatory increase in Alox15 gene expression, and treatment of these mice with the 12/15-lipoxygenase inhibitor ML-351 rescued the dysglycemic phenotype. Collectively, these results indicate that Alox12 loss activates a compensatory increase in Alox15 that sensitizes mouse β cells to oxidative stress.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Lipids Source Type: research