Coordinated expression and mechanism of induction of HSP32 (heme oxygenase-1) mRNA by hyperthermia in rat organs.
Heme oxygenase isozymes, HO-1 and HO-2, catalyze the cleavage of heme b (Fe-protoporphyrin-IX) at the alpha-meso carbon bridge to form the antioxidant, biliverdin IX alpha, and the putative cellular messenger, carbon monoxide. HO-1 is a heat shock (HSP32) or stress protein, while HO-2 is a noninducible enzyme. Presently, we have examined the time course of expression of HSP32 in liver, kidney, and heart of rats exposed to hyperthermia and investigated the mechanism of induction of HO-1 by hyperthermia. We report a coordinated induction response of all organs to elevated ambient temperature (42 degrees C, 20 min). Specifically, the maximum induction of the 1.8 kb HO-1 mRNA was observed 1 h after hyperthermia and reached a value 20-40-fold that of the control; the transcript level approximated the control value by 6 h after heat stress. In contrast, the levels and the ratio of the 1.3 and 1.9 kb HO-2 transcripts were not affected by hyperthermia. As judged by in vitro nuclear transcription run-on assays, thermal stress caused the stimulation of HO-1 gene transcription. The increase in HO-1 mRNA transcription was accompanied by an increase in binding of nuclear factor(s) to the heat shock element in the promoter region of the gene. The increase of the HO-1 mRNA was reflected in increases in both heme oxygenase activity and in immunoreactive HO-1 protein. We suggest that the induction of heme oxygenase by heat stress is a physiologically relevant defense mechanism whereby both the degradation of heme of denatured hemoproteins and the generation of biologically active products of heme catabolism are enhanced.
Raju
V S
VS
Department of Biophysics, University of Rochester, School of Medicine, NY 14642.
Maines
M D
MD
D000818:Animals; D001483:Base Sequence; D004790:Enzyme Induction; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D006358:Hot Temperature; D006979:Hyperthermia, Induced; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing)