Heme oxygenase-1 protects rat kidney from ureteral obstruction via an antiapoptotic pathway.
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.
Kim
Jin Hyun
JH
Department of Internal Medicine, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Chilam-dong 92, Jinju, Gyeongnam 660-751, Republic of Korea.
Yang
Jung Ill
JI
Jung
Myeong Hee
MH
Hwa
Jeong Seok
JS
Kang
Kee Ryeon
KR
Kang
Kee-Ryeong
KR
Park
Dong Jun
DJ
Roh
Gu Seob
GS
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Chang
Se-Ho
SH
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*
D051017:Apoptosis Regulatory Proteins; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat