Group VIB Phospholipase A2 Promotes Proliferation of INS-1 Insulinoma Cells and Attenuates Lipid Peroxidation and Apoptosis Induced by Inflammatory Cytokines and Oxidant Agents. (11th November 2012)

• Record Type: Journal Article
• Authors: Bao, Shunzhong; Song, Haowei; Tan, Min; Wohltmann, Mary; Ladenson, Jack H.; Turk, John
• Other Names: Venditti Paola Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2012(2012)
• Publication Date: 2012-11-11
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2012/989372
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Group VIB Phospholipase A2 (iPLA2 γ ) is distributed in membranous organelles in which β -oxidation occurs, that is, mitochondria and peroxisomes, and is expressed by insulin-secreting pancreatic islet β -cells and INS-1 insulinoma cells, which can be injured by inflammatory cytokines, for example, IL-1 β and IFN- γ, and by oxidants, for example, streptozotocin (STZ) or t-butyl-hydroperoxide (TBHP), via processes pertinent to mechanisms of β -cell loss in types 1 and 2 diabetes mellitus. We find that incubating INS-1 cells with IL-1 β and IFN- γ, with STZ, or with TBHP causes increased expression of iPLA2 γ mRNA and protein. We prepared INS-1 knockdown (KD) cell lines with reduced iPLA2 γ expression, and they proliferate more slowly than control INS-1 cells and undergo increased membrane peroxidation in response to cytokines or oxidants. Accumulation of oxidized phospholipid molecular species in STZ-treated INS-1 cells was demonstrated by LC/MS/MS scanning, and the levels in iPLA2 γ -KD cells exceeded those in control cells. iPLA2 γ -KD INS-1 cells also exhibited higher levels of apoptosis than control cells when incubated with STZ or with IL-1 β and IFN- γ . These findings suggest that iPLA2 γ promotes β -cell proliferation and that its expression is increased during inflammation or oxidative stress as a mechanism to mitigate membrane injury that may enhance β -cell survival.