DNA damage and stress protein synthesis induced by oxidative stress proceed independently in the human premonocytic line U937.
Heat shock proteins (HSPs) function as stress-inducible molecular chaperones and exert protective effects against cellular injury. The induction of the HSPs is considered to be mediated by the presence of abnormal proteins within the cell and/or by classical second messengers. Several lines of evidence have however suggested a relationship between DNA damage, HSP induction and thermotolerance. We investigated whether DNA alterations could represent a common signal for the induction of stress protein synthesis during heat shock or exposure to reactive oxygen species in the human premonocytic line U937. We measured, in parallel, DNA damage (both strand breaks and fragmentation) and HSP synthesis (by biometabolic labeling and Western blotting) after exposure to heat shock, hydrogen peroxide, bleomycin, cadmium or erythrophagocytosis. Heat shock induced DNA alterations along with HSP synthesis. In contrast, exposure to hydrogen peroxide or bleomycin induced DNA damage, but no HSP synthesis, suggesting that oxidation-induced DNA damage and HSP synthesis proceed independently in U937 cells. Erythrophagocytosis and cadmium induced the classical HSPs but no detectable DNA damage. Since these latter stresses also induced the oxidation-specific stress protein heme oxygenase, we suggest a protective role for heme oxygenase against oxidative DNA damage.
Minisini
M P
MP
Allergy Unit, University Hospital, Geneva, Switzerland.
Kantengwa
S
S
Polla
B S
BS
D001761:Bleomycin / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002460:Cell Line; D004249:DNA Damage; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010587:Phagocytosis
D006360:Heat-Shock Proteins; D002104:Cadmium; D001761:Bleomycin; D006861:Hydrogen Peroxide; D002117:Calcitriol