Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels.
Small stress proteins [small heat shock proteins (sHsps)] are molecular chaperones that modulate the ability of cells to respond to oxidative stress. The current knowledge concerning the protective mechanism generated by the expression of mammalian heat shock protein-27 (Hsp27) that allows cells to increase their resistance to oxidative stress is presented. We describe the effects mediated by Hsp27 expression toward crucial enzymes such as glucose-6-phosphate dehydrogenase and glutathione reductase that uphold glutathione in its reduced form. New data are presented showing that the expression of sHsps correlates with a drastic decrease in the intracellular level of iron, a catalyzer of hydroxyl radical (OH( . )) generation. A decreased ability of sHsps expressing cells to concentrate iron will therefore end up in a decreased level of oxidized proteins. In addition, we propose a role of Hsp27 in the presentation of oxidized proteins to the proteasome degradation machinery. We also present an analysis of several Hsp27 mutants that suggests that the C-terminal part of this stress protein is essential for its protective activity against oxidative stress.
Arrigo
André-Patrick
AP
Laboratoire stress oxydant, chaperons et apoptose, Centre de Génétique Moléculaire et Cellulaire, CNRS UMR-5534, Université Claude Bernard, Lyon-I, Bât. Gregor Mendel, 16 rue Dubois, 69622 Villeurbanne Cédex, France. arrigo@univ-lyon1.fr
Virot
Sophie
S
Chaufour
Sylvain
S
Firdaus
Wance
W
Kretz-Remy
Carole
C
Diaz-Latoud
Chantal
C
D000818:Animals; D015536:Down-Regulation; D005978:Glutathione / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D006360:Heat-Shock Proteins; D007501:Iron; D005978:Glutathione