Research work · 2012

Group VIB Phospholipase A_<b>2</b>Promotes Proliferation of INS-1 Insulinoma Cells and Attenuates Lipid Peroxidation and Apoptosis Induced by Inflammatory Cytokines and Oxidant Agents

Shunzhong Bao, Haowei Song, Min Tan, Mary Wohltmann, Jack H. Ladenson

Oxidative Medicine and Cellular Longevity

Abstract

Group VIB Phospholipase A2(iPLA2γ) is distributed in membranous organelles in whichβ-oxidation occurs, that is, mitochondria and peroxisomes, and is expressed by insulin-secreting pancreatic isletβ-cells and INS-1 insulinoma cells, which can be injured by inflammatory cytokines, for example, IL-1βand IFN-γ, and by oxidants, for example, streptozotocin (STZ) or t-butyl-hydroperoxide (TBHP), via processes pertinent to mechanisms ofβ-cell loss in types 1 and 2 diabetes mellitus. We find that incubating INS-1 cells with IL-1βand IFN-γ, with STZ, or with TBHP causes increased expression of iPLA2γmRNA and protein. We prepared INS-1 knockdown (KD) cell lines with reduced iPLA2γexpression, 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 iPLA2γ-KD cells exceeded those in control cells. iPLA2γ-KD INS-1 cells also exhibited higher levels of apoptosis than control cells when incubated with STZ or with IL-1βand IFN-γ. These findings suggest that iPLA2γpromotesβ-cell proliferation and that its expression is increased during inflammation or oxidative stress as a mechanism to mitigate membrane injury that may enhanceβ-cell survival.

DOI: 10.1155/2012/989372