Einfluss von Hitzeschockprotein 70 auf die biliäre Sekretion organischer Anionen bei experimenteller septischer Cholestase

Abstract

Cholestasis and icterus are common problems in sepsis and endotoxemia. Both conditions indicate retention of bile acids and organic anions. These molecules may accumulate in the systemic circulation of within the cytoplasm. Both have been shown to be toxic and capable of inducing necrosis and apoptosis. In previous studies we have shown that heat stress preserves bile acid transport in endotoxemic rats. The aim of the present study was to investigate, if heat stress would also preserve the transport of organic anions. Sulfobromophthalein was used as marker Substrate in experiments determining the maximum transport rate in isolated perfused rat livers. Immunoblot analyses, Northern blot analyses and immunofluorescence microscopy determined the regulation and distribution of the basolateral and canalicular transport proteins. The experiments showed that heat stress is capable to prevent impairment of organic anion transport observed in endotoxemia. Preservation primarily affects the protein level rather than the RNA level. Distribution of transporters was not changed by heat stress. The protective effects of heat stress coincided with the induction of heat shock proteins 70 and 25, supporting a crucial role of these chaperones.