Hsp72 inhibits Fas-mediated apoptosis upstream of the mitochondria in type II cells

J Biol Chem. 2005 Mar 11;280(10):9005-12. doi: 10.1074/jbc.M414165200. Epub 2005 Jan 4.

Abstract

Heat shock protein 72 (Hsp72) inhibits apoptosis induced by some stresses that trigger the intrinsic apoptosis pathway. However, with the exception of TNFalpha-induced apoptosis, a role for Hsp72 in modulating the extrinsic pathway of apoptosis has not been clearly established. In this study, it was demonstrated that Hsp72 could inhibit Fas-mediated apoptosis of type II CCRF-CEM cells, but not type I SW480 or CH1 cells. Similar results were obtained when Fas ligand or an agonistic Fas antibody initiated the Fas apoptosis pathway. In CCRF-CEM cells, Hsp72 inhibited mitochondrial membrane depolarization and cytochrome c release but did not alter surface Fas expression or processing of caspase-8 and Bid, indicating that Hsp72 acts upstream of the mitochondria to inhibit Fas-mediated apoptosis. Thus, the ability of Hsp72 to inhibit Fas-mediated apoptosis is limited to type II cells where involvement of the intrinsic pathway is required for efficient effector caspase activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis / drug effects*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cysteine Proteinase Inhibitors / pharmacology
  • HSP72 Heat-Shock Proteins
  • Heat-Shock Proteins / physiology*
  • Humans
  • Mitochondria / physiology*
  • fas Receptor / physiology*

Substances

  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • HSP72 Heat-Shock Proteins
  • Heat-Shock Proteins
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • fas Receptor
  • Caspases