Phospholipases A2 (PLA2s) is enzymes that cleave fatty acid in position two of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glycerol molecule. Peroxiredoxin 6 (Prdx6) has the endogenous antioxidant protein for its peroxide properties. Prdx6 is the uniquely 1-Cys member of the peroxiredoxin family with both GSH peroxidase and calcium-independent phospholipase A2 (iPLA2) activities. Specifically, the Prdx6-iPLA2 activity is as giving off potent proinflammatory signals. In human bronchial epithelial cells (BEAS2B), the production of interleukin-1β (IL-1β) was dependent on the iPLA2 activity of Prdx6. Besides, Prdx6-iPLA2 activity was associated with lung inflammation through the activation of NADPH oxidase (NOX2). Moreover, the iPLA2 activity of Prdx6 may be involved in proinflammatory stimuli. Interestingly, PRDX6 can reduce phospholipid hydroperoxides as well and has Ca2+-iPLA2 and lysophospholipid acyltransferase activities. MJ33 is a specific and competitive peroxiredoxin 6 -independent phospholipase A2 (Prdx6-iPLA2) activity inhibitor.
MJ33 is a specific and competitive phospholipase A2 (PLA2) activity inhibitor with anti-inflammatory activities. In addition, MJ33 could significantly protect the lung against damage from hyperoxia. In vivo, combined treatment with Prdx6-iPLA2 activity inhibitor MJ33 showed a greater diminution in neurologic deficits, cerebral infarction, brain water content and inflammatory molecules. Meanwhile, MJ33 inhibited the PRDX6 Ca2+-iPLA2 activity and reduced these parameters in WT spermatozoa compared with controls. MJ33 increased the levels of lipid peroxidation and mitochondrial O2 •─ production in treated versus non-treated WT spermatozoa. Nonetheless, MJ33 resulted in a significant decrease of iPLA2 activity compared with the Scramble group. All in all, MJ33 is a specific and competitive PLA2 activity inhibitor.