Journal
CELL DEATH AND DIFFERENTIATION
Volume 8, Issue 4, Pages 357-366Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4400829
Keywords
apoptosis; DnaJ homolog; macrophage; molecular chaperone; nitric oxide
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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, di1 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.
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