title: Heat shock suppresses the permeability transition in rat liver mitochondria.
abstract: Heat shock proteins inhibit apoptotic and necrotic cell death in various cell types. However, the specific mechanism underlying protection by heat shock proteins remains unclear. To test the hypothesis that heat shock proteins inhibit cell death by blocking opening of mitochondrial permeability transition (MPT) pores, mitochondria from heat-preconditioned rat livers were isolated by differential centrifugation. Heat shock inhibited MPT pore opening induced by 50 microm CaCl(2) plus 5 microm HgCl(2) or 1 microm mastoparan and by 200 microm CaCl(2) alone. Half-maximal swelling was delayed 15 min or more after heat shock compared with control. Heat shock also increased the threshold of unregulated (Ca(2+)-independent and cyclosporin A-insensitive) MPT pore opening induced by higher doses of HgCl(2) and mastoparan. Heat shock treatment decreased mitochondrial reactive oxygen species formation by 27% but did not change mitochondrial respiration, membrane potential, Ca(2+) uptake, or total glutathione in mitochondrial and cytosolic extracts of liver. Western blot analysis showed that mitochondrial Hsp25 increased, whereas Hsp10, Hsp60, Hsp70, Hsp75, cyclophilin D, and voltage-dependent anion channel did not change after heat shock. These results indicate that heat shock causes resistance to opening of MPT pores, which may contribute to heat shock protection against cellular injury.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599-7090, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: He
authors.forename: John J
authors.initials: JJ
authors.lastname: Lemasters
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D006358:Hot Temperature; D008297:Male; D008930:Mitochondria, Liver / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006360:Heat-Shock Proteins