DIFFERENTIAL ACTIVATION OF HEAT-SHOCK AND OXIDATION-SPECIFIC STRESS GENES IN CHEMICALLY-INDUCED OXIDATIVE STRESS

Post-ischaemic reperfusion increases the levels of the major heat-shoc k (stress) protein hsp 70 and of its mRNA by transcriptional mechanism s, and activates the binding of the heat-shock factor HSF to the conse nsus sequence HSE. In common with CoCl2 treatment, post-ischaemic repe rfusion increases the level of haem oxygenase mRNA, an indicator of ox idative stress, but CoCl2, does not seem to induce the expression of t he hsp 70 gene [Tacchini, Schiaffonati, Pappalardo, Gatti and Bernelli -Zazzera (1993) Lab. Invest. 68, 465-471]. Starting from these observa tions, we have now studied the expression of two genes of the hsp 70 f amily and of other possibly related genes under conditions of oxidativ e stress. Three different chemicals, which cause oxidative stress by v arious mechanisms and induce haem oxygenase, enhance the expression of the cognate hsc 73 gene, but do not activate the inducible hsp 70 gen e. Expression of the other genes that have been studied seems to vary in intensity and/or time course, in relation to the particular mechani sm of action of any single agent. The pattern of induction of the earl y-immediate response genes c-fos and c-jun observed during oxidative s tress differs from that found in post-ischaemic reperfused livers. Oxi dative-stress-inducing agents do not promote the binding of HSF to its consensus sequence HSE, such as occurs in heat-shock and post-ischaem ic reperfusion, and fail to activate AP-1 (activator protein 1). With the possible exception of Phorone, the oxidative stress chemically ind uced in rat liver activates NFkB (nuclear factor kB) and AP-2 (activat or protein 2) transcription factors.