title: hsp70-DnaJ chaperone pairs prevent nitric oxide-mediated apoptosis in RAW 264.7 macrophages.
abstract: Excess nitric oxide (NO) induces apoptosis in some cell types, including macrophages. Heat shock protein of 70 kDa (hsp70) has been reported to protect cells from various stresses, including apoptosis-inducing stimuli. Several mammalian cytosolic DnaJ homologs, partner chaperones of hsp70 family members, have been identified. We asked if a DnaJ homolog is required to prevent NO-mediated apoptosis. When mouse macrophage-like RAW 264.7 cells were treated with an NO donor, SNAP, apoptosis occurred. This apoptosis could be prevented by pretreatment of the cells with heat or a low dose of SNAP. Under these conditions, levels of hsc70 (an hsp70 member) remained unchanged, whereas hsp70 was markedly induced. Of the DnaJ homologs dj1 (hsp40/hdj-1) was strongly induced and dj2 (HSDJ/hdj-2) was moderately induced. In transfection experiments, hsp70, hsc70, dj1 or dj2 alone was ineffective in preventing NO-mediated apoptosis. In contrast, both dj1 and dj2, in combination with hsc70 or hsp70, prevented the cells from apoptosis. The hsp70-DnaJ chaperone pairs exerted their anti-apoptotic effects upstream of caspase 3 activation, and apparently upstream of cytochrome c release from mitochondria.
authors.affiliation: Department of Molecular Genetics, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860-0811, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Gotoh
authors.forename: K
authors.initials: K
authors.lastname: Terada
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D018869:Heat-Shock Response; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D003574:Cytochrome c Group; C107481:DNAJA1 protein, human; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D010396:Penicillamine