Hsp70-DnaJ chaperone pairs prevent nitric oxide-mediated apoptosis in RAW 264.7 macrophages

Citation
T. Gotoh et al., Hsp70-DnaJ chaperone pairs prevent nitric oxide-mediated apoptosis in RAW 264.7 macrophages, CELL DEAT D, 8(4), 2001, pp. 357-366
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL DEATH AND DIFFERENTIATION
ISSN journal
1350-9047 → ACNP
Volume
8
Issue
4
Year of publication
2001
Pages
357 - 366
Database
ISI
SICI code
1350-9047(200104)8:4<357:HCPPNO>2.0.ZU;2-C
Abstract
Excess nitric oxide (NO) induces apoptosis in some cell types, including ma crophages, Heat shock protein of 70 kDa (hsp70) has been reported to protec t cells from various stresses, including apoptosis-inducing stimuli. Severa l mammalian cytosolic DnaJ homologs, partner chaperones of hsp70 family mem bers, have been identified. We asked if a DnaJ homolog is required to preve nt NO-mediated apoptosis. When mouse macrophage-like RAW 264.7 cells were t reated 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. Und er 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 transf ection experiments, hsp70, hsc70, di1 or dj2 alone was ineffective in preve nting NO-mediated apoptosis, In contrast, both dj1 and dj2, in combination with hsc70 or hsp70, prevented the cells from apoptosis, The hsp70-DnaJ cha perone pairs exerted their anti-apoptotic effects upstream of caspase 3 act ivation, and apparently upstream of cytochrome c release from mitochondria.