Induction of group VIA phospholipase A2 activity during in vitro ischemia in C2C12 myotubes is associated with changes in the level of its splice variants.

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Abstract

The involvement of group VI Ca(2+)-independent PLA(2)s (iPLA(2)-VI) in in vitro ischemia [oxygen and glucose deprivation (OGD)] in mouse C2C12 myotubes was investigated. OGD induced a time-dependent (0-6 h) increase in bromoenol lactone (BEL)-sensitive iPLA(2) activity, which was suppressed by specific short interfering (si)RNA knockdown of iPLA(2)-VIA. OGD was associated with an increase in iPLA(2)-VIA protein levels, whereas mRNA levels were unchanged. The levels of iPLA(2)-VIB mRNA and protein were not increased by OGD. RT-PCR and Western blot analysis identified a mouse iPLA(2)-VIA homolog to catalytically inactive 50-kDa iPLA(2)-VIA-ankyrin variants previously identified in humans. Both the mRNA and protein levels of this approximately 50-kDa variant were reduced significantly within 1 h following OGD. In C2C12 myoblasts, iPLA(2)-VIA seemed to predominantly reside at the endoplasmatic reticulum, where it accumulated further during OGD. A time-dependent reduction in cell viability during the early OGD period (3 h) was partially prevented by iPLA(2)-VIA knockdown or pharmacological inhibition (10 microM BEL), whereas iPLA(2)-VIA overexpression had no effect on cell viability. Taken together, these data demonstrate that OGD in C2C12 myotubes is associated with an increase in iPLA(2)-VIA activity that decreases cell viability. iPLA(2)-VIA activation may be modulated by changes in the levels of active and inactive iPLA(2)-VIA isoforms.
Udgivelsesdato: 2007-Nov
Original languageEnglish
JournalAmerican Journal of Physiology: Cell Physiology
Volume293
Issue number5
Pages (from-to)C1605-15
ISSN0363-6143
DOIs
Publication statusPublished - 2007

Bibliographical note

Keywords: Animals; Arachidonic Acids; Cell Hypoxia; Cell Line; Cell Survival; Endoplasmic Reticulum; Enzyme Induction; Glucose; Group IV Phospholipases A2; Ischemia; Mice; Molecular Weight; Muscle Fibers; Muscle, Skeletal; Naphthalenes; Phosphodiesterase Inhibitors; Protein Isoforms; Pyrones; RNA Interference; RNA, Messenger; RNA, Small Interfering; Time Factors

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