Expression of HSP 70, immediate-early response and heme oxygenase genes in ischemic-reperfused rat liver.
BACKGROUND
Reperfusion of the liver after non-necrogenic ischemia induces the expression of the HSP gene and the synthesis of the hsp 70 protein, the best known among stress (heat-shock) proteins.


METHODS
We have studied the time course of the induction and the effects of cycloheximide treatment on the expression of c-fos, c-jun and the heat-shock gene HSP 70 in ischemic-reperfused livers; extracts of these livers have also been examined for the binding to a synthetic oligonucleotide containing the heat-shock consensus sequence (HSE) in order to reveal the possible presence of an active heat-shock factor (HSF) in ischemic-reperfused tissue.


RESULTS
Expression of HSP 70 gene appears only after a certain threshold of cell damage, is preceded by induction of c-fos and c-jun but does not depend on ongoing protein synthesis. The binding of HSF to HSE seems to start during the late period of ischemia, although the subsequent reperfusion increases the effect. The level of heme-oxygenase mRNA, an indicator of oxidative stress, increases in the liver after reperfusion but the oxidative stress caused by CoCl2 treatment does not induce the expression of HSP 70 gene under the conditions of the present experiments.


CONCLUSIONS
We suggest that, similar to heat-shock, protein malfolding occurring during ischemia may trigger the HSP 70 gene induction, which is then amplified by the subsequent reperfusion stress. A model of chemically induced oxidative stress seems to be unable to induce the HSP 70 gene expression with the same characteristics of heat shock or ischemia-reperfusion.
Tacchini
L
L
Istituto di Patologia Generale, Universitå degli Studi di Milano, Italy.
Schiaffonati
L
L
Pappalardo
C
C
Gatti
S
S
Bernelli-Zazzera
A
A
D000818:Animals; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D066298:In Vitro Techniques; D007511:Ischemia / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015424:Reperfusion; D013997:Time Factors
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing)