title: Group VIB Phospholipase A(2) promotes proliferation of INS-1 insulinoma cells and attenuates lipid peroxidation and apoptosis induced by inflammatory cytokines and oxidant agents.
abstract: Group VIB Phospholipase A(2) (iPLA(2)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-1β 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-1β and IFN-γ, with STZ, or with TBHP causes increased expression of iPLA(2)γ mRNA and protein. We prepared INS-1 knockdown (KD) cell lines with reduced iPLA(2)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 iPLA(2)γ-KD cells exceeded those in control cells. iPLA(2)γ-KD INS-1 cells also exhibited higher levels of apoptosis than control cells when incubated with STZ or with IL-1β and IFN-γ. These findings suggest that iPLA(2)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.
authors.affiliation: Mass Spectrometry Resource, Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine, Washington University School of Medicine, Campus Box 8127, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Shunzhong
authors.initials: S
authors.lastname: Bao
authors.forename: Haowei
authors.initials: H
authors.lastname: Song
authors.forename: Min
authors.initials: M
authors.lastname: Tan
authors.forename: Mary
authors.initials: M
authors.lastname: Wohltmann
authors.forename: Jack H
authors.initials: JH
authors.lastname: Ladenson
authors.forename: John
authors.initials: J
authors.lastname: Turk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D054522:Group VI Phospholipases A2 / Q000378:metabolism*; D018836:Inflammation Mediators / Q000494:pharmacology; D007340:Insulinoma / Q000201:enzymology* / Q000473:pathology*; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000737:chemistry; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013311:Streptozocin / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008055:Lipids; D016877:Oxidants; D013311:Streptozocin; D007371:Interferon-gamma; D020122:tert-Butylhydroperoxide; D054522:Group VI Phospholipases A2