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Intracellular K+ inhibits apoptosis by suppressing the Apaf-1 apoptosome formation and subsequent downstream pathways but not cytochrome c release

Title
Intracellular K+ inhibits apoptosis by suppressing the Apaf-1 apoptosome formation and subsequent downstream pathways but not cytochrome c release
Authors
Karki P.Seong C.Kim J.-E.Hur K.Shin S.Y.Lee J.S.Cho B.Park I.-S.
Ewha Authors
허규정
SCOPUS Author ID
허규정scopus
Issue Date
2007
Journal Title
Cell Death and Differentiation
ISSN
1350-9047JCR Link
Citation
vol. 14, no. 12, pp. 2068 - 2075
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Cellular ionic homeostasis, fundamentally K+ homeostasis, has been implicated as a critical regulator of apoptosis. The intracellular K+ efflux on apoptotic insult and suppression of apoptosis by high concentration of extracellular K+ or after inhibition of this efflux by K+ channel blockers have established the crucial role of K+ in turning on the apoptotic machinery. Several contrasting observations have reported the antiapoptotic effect of intracellular K+ concentration to be the result of inhibition of cytochrome c release from mitochondria, but the exact inhibitory mechanism remains obscure. However, here we show the blockage of K+ efflux during apoptosis did not affect cytochrome c release from the mitochondria, still completely inhibited the formation of the apoptosome comprising Apaf-1, cytochrome c, caspase-9 and other accessories. As a consequence of this event, procaspase-9, -3, -8 and other death-related proteins were not processed. Furthermore, physiological concentrations of K+ also inhibited the processing of procaspase-3 by purified caspase-8 or -9, the nucleosomal DNA fragmentation by purified DFF40/CAD and the nuclear fragmentation to varying extents. Altogether, these findings suggest that the efflux of K+ is prerequisite not only for the formation of the apoptosome but also for the downstream apoptotic signal-transduction pathways.
DOI
10.1038/sj.cdd.4402221
Appears in Collections:
일반대학원 > 바이오융합과학과 > Journal papers
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