title: Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32.
abstract: Presently we describe, for the first time, induction of microsomal heme oxygenase-1 (HO-1) mRNA and protein in response to ischemia/reperfusion and therefore define HO-1 as stress protein in the kidney. Specifically, Northern blot analysis of kidneys of rats subjected to bilateral ischemia for 30 min revealed an increase of 8- to 10-fold in the level of 1.8 Kb HO-1 mRNA 6 hr after reperfusion. The increase in transcript level was maintained when assessed after 24 hr. The levels of 1.3 and 1.9 Kb transcripts for the second isozyme of HO, HO-2, were decreased at both time points. The increase in HO-1 mRNA was reflected in HO-1 protein level, as judged by Western blot analysis and at the level of activity as judged by the rate of bilirubin formation. An absence of change in adrenal HO-1 mRNA level subsequent to renal ischemia/reperfusion suggested that the induction of kidney HO-1 did not reflect a generalized response of the rat organs to stress; rather, it was a target organ specific response. Moreover, in kidneys subjected to ischemia 6 and 24 hr after reperfusion, significant increases in the cellular content of heme were observed; heme is a known inducer of HO-1 synthesis. Ischemia/reperfusion also adversely affected concentration of cytochrome P-450 in both mitochondrial and the microsomal fractions of the kidney. We suggest that increase in tissue heme levels may be a significant factor in damage caused by ischemia/reperfusion to renal tissue, whereby the metalloporphyrin promotes oxygen-free radical formation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: University of Rochester School of Medicine, Department of Biophysics, New York.
authors.forename: M D
authors.initials: MD
authors.lastname: Maines
authors.forename: R D
authors.initials: RD
authors.lastname: Mayer
authors.forename: J F
authors.initials: JF
authors.lastname: Ewing
authors.forename: W K
authors.initials: WK
authors.lastname: McCoubrey
mesh_terms: D000818:Animals; D001654:Bile Pigments / Q000378:metabolism; D015152:Blotting, Northern; D004790:Enzyme Induction; D006418:Heme / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D007511:Ischemia / Q000201:enzymology* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology* / Q000502:physiology; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000009:adverse effects
chemical_list: D001654:Bile Pigments; D007527:Isoenzymes; D012333:RNA, Messenger; D006418:Heme; D006419:Heme Oxygenase (Decyclizing)