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: Shunzhong Bao, Haowei Song, Min Tan, Mary Wohltmann, Jack H Ladenson, John Turk
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2012 Pg. 989372 ( 2012) ISSN: 1942-0994 [Electronic] United States
• PMID: 23213352 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Inflammation Mediators
• Interleukin-1beta
• Lipids
• Oxidants
• Streptozocin
• Interferon-gamma
• tert-Butylhydroperoxide
• Group VI Phospholipases A2

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chromatography, High Pressure Liquid
• Cytokines (pharmacology)
• Gene Knockdown Techniques
• Group VI Phospholipases A2 (metabolism)
• Inflammation Mediators (pharmacology)
• Insulinoma (enzymology, pathology)
• Interferon-gamma (pharmacology)
• Interleukin-1beta (pharmacology)
• Lipid Peroxidation (drug effects)
• Lipids (chemistry)
• Oxidants (pharmacology)
• Oxidation-Reduction (drug effects)
• Rats
• Spectrometry, Mass, Electrospray Ionization
• Streptozocin (pharmacology)
• tert-Butylhydroperoxide (pharmacology)