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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
- 허규정
- Issue Date
- 2007
- Journal Title
- Cell Death and Differentiation
- ISSN
- 1350-9047
- Citation
- Cell Death and Differentiation vol. 14, no. 12, pp. 2068 - 2075
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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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