Differential activation of heat-shock and oxidation-specific stress genes in chemically induced oxidative stress.
Post-ischaemic reperfusion increases the level of the major heat-shock (stress) protein hsp 70 and of its mRNA by transcriptional mechanisms, and activates the binding of the heat-shock factor HSF to the consensus sequence HSE. In common with CoCl2 treatment, post-ischaemic reperfusion increases the level of haem oxygenase mRNA, an indicator of oxidative stress, but CoCl2 does not seem to induce the expression of the hsp 70 gene [Tacchini, Schiaffonati, Pappalardo, Gatti and Bernelli-Zazzera (1993) Lab. Invest. 68, 465-471]. Starting from these observations, we have now studied the expression of two genes of the hsp 70 family and of other possibly related genes under conditions of oxidative stress. Three different chemicals, which cause oxidative stress by various mechanisms and induce haem oxygenase, enhance the expression of the cognate hsc 73 gene, but do not activate the inducible hsp 70 gene. Expression of the other genes that have been studied seems to vary in intensity and/or time course, in relation to the particular mechanism of action of any single agent. The pattern of induction of the early-immediate response genes c-fos and c-jun observed during oxidative stress differs from that found in post-ischaemic reperfused livers. Oxidative-stress-inducing agents do not promote the binding of HSF to its consensus sequence HSE, such as occurs in heat-shock and post-ischaemic reperfusion, and fail to activate AP-1 (activator protein 1). With the possible exception of Phorone, the oxidative stress chemically induced in rat liver activates NFkB (nuclear factor kB) and AP-2 (activator protein 2) transcription factors.
Tacchini
L
L
Istituto di Patologia Generale dell'Università degli Studi di Milano, Centro di Studio sulla Patologia Cellulare del CNR, Italy.
Pogliaghi
G
G
Radice
L
L
Anzon
E
E
Bernelli-Zazzera
A
A
D000818:Animals; D001483:Base Sequence; D019328:Buthionine Sulfoximine; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D007659:Ketones / Q000494:pharmacology; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008969:Molecular Sequence Data; D009582:Nitrofurantoin / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar
D018840:HSP70 Heat-Shock Proteins; D007659:Ketones; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C018637:phorone; D009582:Nitrofurantoin; D005721:Glutamate-Cysteine Ligase