Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide

Toshihiro Mochizuki, Akio Asai, Nobuhito Saito, Sakae Tanaka, Hideki Katagiri, Tomoichiro Asano, Makoto Nakane, Akira Tamura, Yoshiyuki Kuchino, Chifumi Kitanaka, Takaaki Kirino

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

A growing body of evidence now suggests that programmed cell death (PCD) occurs via non-apoptotic mechanisms as well as by apoptosis. In contrast to apoptosis, however, the molecular mechanisms involved in the regulation of non-apoptotic PCD remain only poorly understood. Here we show that ceramide induces a nonapoptotic PCD with a necrotic-like morphology in human glioma cells. Characteristically, the cell death was not accompanied by loss of the mitochondrial transmembrane potential, cytosolic release of cytochrome c from mitochondria, or the activation of the caspase cascade. Consistent with these characteristics, this ceramide-induced cell death was inhibited neither by the overexpression of Bcl-xL nor by the pan-caspase inhibitor zVAD-fmk. However, strikingly, the ceramide-induced non-apoptotic cell death was inhibited by the activation of the Akt/protein kinase B pathway through the expression of a constitutively active version of Akt. The results for the first time indicate that the Akt kinase, known to play an essential role in survival factor-mediated inhibition of apoptotic cell death, is also involved in the regulation of non-apoptotic PCD.

Original languageEnglish
Pages (from-to)2790-2797
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number4
DOIs
Publication statusPublished - 2002 Jan 25
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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