详细记录  
题名:Group VIA Phospholipase A2 Mitigates Palmitate-Induced Beta Cell Mitochondrial Injury and Apoptosis.
作者:SONG H; WOHLTMANN M; TAN M; LADENSON JH; TURK J;
来源:J Biol Chem. 2014 Mar 19. [ IF= 0.00 ] ]
URL :10.1074/jbc.M114.561910
日期:20140408
摘要:Palmitate (C16:0) induces apoptosis of insulin-secreting beta-cells by processes
that involve generation of reactive oxygen species (ROS), and chronically
elevated blood long chain free fatty acid (FFA) levels are thought to contribute
to beta-cell lipotoxicity and the development of diabetes mellitus. Group VIA
phospholipase A2 (iPLA2beta) affects beta-cell sensitivity to apoptosis, and here
we examined iPLA2beta effects on events that occur in beta-cells incubated with
C16:0. Such events in INS-1 insulinoma cells were found to include activation of
caspase-3, expression of stress response genes (CHOP and ATF4), accumulation of
ceramide, loss of mitochondrial membrane potential, and apoptosis. All of these
responses were blunted in INS-1 cells that overexpress iPLA2beta, which has been
proposed to facilitate repair of oxidized mitochondrial phospholipids, e.g.,
cardiolipin (CL), by excising oxidized polyunsaturated fatty acid residues, e.g.,
linoleate (C18:2), to yield lysophospholipids, e.g., monolysocardiolipin (MLCL),
that can be reacylated to regenerate the native phospholipid structures. Here,
the MLCL content of mouse pancreatic islets was found to rise with increasing
iPLA2beta expression, and recombinant iPLA2beta hydrolyzed CL to MLCL and
released oxygenated-C18:2 residues from oxidized CL in preference to native
C18:2. C16:0 induced accumulation of oxidized CL species and of the oxidized
phospholipid (C18:0/HETE)-GPE, and these effects were blunted in INS-1 cells that
overexpress iPLA2beta, consistent with iPLA2beta-mediated removal of oxidized
phospholipids. C16:0 also induced iPLA2beta association with INS-1 cell
mitochondria, consistent with a role in mitochondrial repair. These findings
indicate that iPLA2beta confers significant protection of beta-cells against
C16:0-induced injury.

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