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 ind uces the expression of the HSP gene and the synthesis of the hsp 70 pr otein, the best known among stress (heat-shock) proteins. EXPERIMENTAL DESIGN: We have studied the time course of the induction and the effe cts of cycloheximide treatment on the expression of c-fos, c-jun and t he heat-shock gene HSP 70 in ischemic-reperfused livers; extracts of t hese livers have also been examined for the binding to a synthetic oli gonucleotide containing the heat-shock consensus sequence (HSE) in ord er to reveal the possible presence of an active heat-shock factor (HSF ) in ischemic-reperfused tissue. RESULTS: Expression of HSP 70 gene ap pears only after a certain threshold of cell damage, is preceded by in duction of c-fos and c-jun but does not depend on ongoing protein synt hesis. 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 caus ed by CoCl2 treatment does not induce the expression of HSP 70 gene un der the conditions of the present experiments. CONCLUSIONS: We suggest that, similar to heat-shock, protein malfolding occurring during isch emia may trigger the HSP 70 gene induction, which is then amplified by the subsequent reperfusion stress. A model of chemically induced oxid ative stress seems to be unable to induce the HSP 70 gene expression w ith the same characteristics of heat shock or ischemia-reperfusion.