title: Heme oxygenase-1 protects rat kidney from ureteral obstruction via an antiapoptotic pathway.
abstract: This study examined the functional significance of heme oxygenase-1 (HO-1) expression on renal injury induced by ureteral obstruction in the rat kidney. Male Sprague-Dawley rats were divided into three groups, after which unilateral ureteral obstruction (UUO) was performed: untreated (group 1), treated with 30 mg/kg body wt hemin (group 2), and treated with 50 microg/kg body wt zinc (alpha) protoporphyrin eta (ZnPP) and 30 mg/kg hemin (group 3). After 7 and 14 d, histologic changes and the expression of HO-1, Bcl-2, Bad, TGF-beta, and cleaved caspase-3 were examined. Tubular lumens were dilated and epithelial cells were flattened on day 7 after UUO. Interstitial fibrosis and separation of the tubules were markedly increased on day 14. In contrast, the kidneys that were treated with hemin exhibited minimal interstitial fibrosis and flattening of epithelial cells on day 7 and fewer changes on day 14 than in the controls. However, treatment with ZnPP, an inhibitor of HO enzyme activity, eliminated the beneficial effect of hemin on interstitial fibrosis and tubular dilation. Increased HO-1 expression was associated with increased Bcl-2. In the ZnPP-treated rats, Bcl-2 signals were decreased compared with the hemin group. The level of proapoptotic Bad was not changed in any group. The positive cells for cleaved caspase-3 were significantly increased in renal tubular epithelial cells and tubulointerstitial cells in the obstructed rats, and hemin treatment decreased the caspase-3 activation. This study demonstrates that upregulation of HO-1 provides protection against renal injury that follows UUO. This effect is dependent on modulation of the antiapoptotic pathway by HO-1 expression.
authors.affiliation: Department of Internal Medicine, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Chilam-dong 92, Jinju, Gyeongnam 660-751, Republic of Korea.
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jung Ill
authors.initials: JI
authors.lastname: Yang
authors.forename: Myeong Hee
authors.initials: MH
authors.lastname: Jung
authors.forename: Jeong Seok
authors.initials: JS
authors.lastname: Hwa
authors.forename: Kee Ryeon
authors.initials: KR
authors.lastname: Kang
authors.forename: Kee-Ryeong
authors.initials: KR
authors.lastname: Kang
authors.forename: Dong Jun
authors.initials: DJ
authors.lastname: Park
authors.forename: Gu Seob
authors.initials: GS
authors.lastname: Roh
authors.forename: Gyeong Jae
authors.initials: GJ
authors.lastname: Cho
authors.forename: Wan Sung
authors.initials: WS
authors.lastname: Choi
authors.forename: Se-Ho
authors.initials: SH
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D009401:Nephrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat