open access

https://hdl.handle.net/2115/718

Gelsolin Inhibits Apoptosis by Blocking Mitochondrial Membrane Potential Loss and Cytochrome c Release

英語

2000-05-19

The American Society for Biochemistry and Molecular Biology

Journal of Biological Chemistry

275(20)

15343-15349

http://www.jbc.org/

Apoptotic cell death, characterized by chromatin condensation, nuclear fragmentation, cell membrane blebbing, and apoptotic body formation, is also accompanied by typical mitochondrial changes. The latter includes enhanced membrane permeability, fall in mitochondrial membrane potential (m) and release of cytochrome c into the cytosol. Gelsolin, an actin regulatory protein, has been shown to inhibit apoptosis, but when cleaved by caspase-3, a fragment that is implicated as an effector of apoptosis is generated. The mechanism by which the full-length form of gelsolin inhibits apoptosis is unclear. Here we show that the overexpression of gelsolin inhibits the loss of m and cytochrome c release from mitochondria resulting in the lack of activation of caspase-3, -8,and -9in Jurkat cells treated with staurosporine, thapsigargin, and protoporphyrin IX. These effects were corroborated in vitro using recombinant gelsolin protein on isolated rat mitochondria stimulated with Ca2+, atractyloside, or Bax. This protective function of gelsolin, which was not due to simple Ca2+ sequestration, was inhibited by polyphosphoinositide binding. In addition we confirmed that gelsolin, besides its localization in the cytosol, is also present in the mitochondrial fraction of cells. Gelsolin thus acts on an early step in the apoptotic signaling at the level of mitochondria.

学術雑誌論文

Accepted Manuscript

Copyright (c) 2000 by the American Society for Biochemistry and Molecular Biology.

00219258