PMID- 23213352 OWN - NLM STAT- MEDLINE DCOM- 20130403 LR - 20230429 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2012 DP - 2012 TI - 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. PG - 989372 LID - 10.1155/2012/989372 [doi] LID - 989372 AB - Group VIB Phospholipase A(2) (iPLA(2)gamma) is distributed in membranous organelles in which beta-oxidation occurs, that is, mitochondria and peroxisomes, and is expressed by insulin-secreting pancreatic islet beta-cells and INS-1 insulinoma cells, which can be injured by inflammatory cytokines, for example, IL-1beta and IFN-gamma, and by oxidants, for example, streptozotocin (STZ) or t-butyl-hydroperoxide (TBHP), via processes pertinent to mechanisms of beta-cell loss in types 1 and 2 diabetes mellitus. We find that incubating INS-1 cells with IL-1beta and IFN-gamma, with STZ, or with TBHP causes increased expression of iPLA(2)gamma mRNA and protein. We prepared INS-1 knockdown (KD) cell lines with reduced iPLA(2)gamma 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)gamma-KD cells exceeded those in control cells. iPLA(2)gamma-KD INS-1 cells also exhibited higher levels of apoptosis than control cells when incubated with STZ or with IL-1beta and IFN-gamma. These findings suggest that iPLA(2)gamma promotes beta-cell proliferation and that its expression is increased during inflammation or oxidative stress as a mechanism to mitigate membrane injury that may enhance beta-cell survival. FAU - Bao, Shunzhong AU - Bao S AD - 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. FAU - Song, Haowei AU - Song H FAU - Tan, Min AU - Tan M FAU - Wohltmann, Mary AU - Wohltmann M FAU - Ladenson, Jack H AU - Ladenson JH FAU - Turk, John AU - Turk J LA - eng GR - R37 DK034388/DK/NIDDK NIH HHS/United States GR - P60-DK20579/DK/NIDDK NIH HHS/United States GR - P30 DK056341/DK/NIDDK NIH HHS/United States GR - 5 T32 DK007120/DK/NIDDK NIH HHS/United States GR - R37-DK34388/DK/NIDDK NIH HHS/United States GR - T32 DK007120/DK/NIDDK NIH HHS/United States GR - P60 DK020579/DK/NIDDK NIH HHS/United States GR - P30 DK020579/DK/NIDDK NIH HHS/United States GR - P41 RR000954/RR/NCRR NIH HHS/United States GR - P41-RR00954/RR/NCRR NIH HHS/United States GR - P30-DK56341/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20121111 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1beta) RN - 0 (Lipids) RN - 0 (Oxidants) RN - 5W494URQ81 (Streptozocin) RN - 82115-62-6 (Interferon-gamma) RN - 955VYL842B (tert-Butylhydroperoxide) RN - EC 3.1.1.4 (Group VI Phospholipases A2) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Chromatography, High Pressure Liquid MH - Cytokines/*pharmacology MH - Gene Knockdown Techniques MH - Group VI Phospholipases A2/*metabolism MH - Inflammation Mediators/pharmacology MH - Insulinoma/*enzymology/*pathology MH - Interferon-gamma/pharmacology MH - Interleukin-1beta/pharmacology MH - Lipid Peroxidation/*drug effects MH - Lipids/chemistry MH - Oxidants/*pharmacology MH - Oxidation-Reduction/drug effects MH - Rats MH - Spectrometry, Mass, Electrospray Ionization MH - Streptozocin/pharmacology MH - tert-Butylhydroperoxide/pharmacology PMC - PMC3503447 EDAT- 2012/12/06 06:00 MHDA- 2013/04/04 06:00 PMCR- 2012/11/11 CRDT- 2012/12/06 06:00 PHST- 2012/06/27 00:00 [received] PHST- 2012/08/20 00:00 [accepted] PHST- 2012/12/06 06:00 [entrez] PHST- 2012/12/06 06:00 [pubmed] PHST- 2013/04/04 06:00 [medline] PHST- 2012/11/11 00:00 [pmc-release] AID - 10.1155/2012/989372 [doi] PST - ppublish SO - Oxid Med Cell Longev. 2012;2012:989372. doi: 10.1155/2012/989372. Epub 2012 Nov 11.