title: Targeted suppression of heme oxygenase-1 by small interference RNAs inhibits the production of bilirubin in neonatal rat with hyperbilirubinemia.
abstract: BACKGROUND
  Excessive accumulation of bilirubin contributes to neonatal hyperbilirubinemia in rats. Heme oxygenase (HO) is one of the rate-limiting enzymes in catabolizing heme to bilirubin. In the present study, we investigated whether suppression of rat HO-1 (rHO-1) expression by small interference RNAs (siRNAs) reduces bilirubin levels in hyperbilirubinemic rats.
  
  
  RESULTS
  Four pairs of siRNA targeting rHO-1 mRNA were introduced into BRL cells and compared for their inhibitory effect on the expression of rHO-1 gene and production of rHO-1 protein. The siRNA exhibiting the most potent effect on HO-1 expression and activity was then administered intraperitoneally to 7 to 9-day-old rats with hyperbilirubinemia. The siRNA distributed mostly in the liver and spleen of neonatal rat. Serum bilirubin levels and hepatic HO-1 expression were further evaluated. Systemic treatment of siRNA targeting rHO-1 reduced hepatic HO-1 expression and decreased the serum bilirubin levels in a time- and dose-dependent manner, and siRNA decreased the indirect bilirubin levels more effectively than Sn-protoporphyrin (SnPP), an HO-1 inhibitor.
  
  
  CONCLUSIONS
  siRNA targeting rHO-l attenuates hepatic HO-1 expression and serum bilirubin levels. Thus this study provides a novel therapeutic rationale for the prevention and treatment of neonatal hyperbilirubinemia.
authors: Ruijin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China. chach84@sina.com
authors: Jinyong
authors: J
authors: Wu
authors: Wen
authors: W
authors: Su
authors: Youxin
authors: Y
authors: Jin
authors: Yi
authors: Y
authors: Shi
authors: Chune
authors: C
authors: Li
authors: Wenwei
authors: W
authors: Zhong
authors: Xuehong
authors: X
authors: Zhang
authors: Zili
authors: Z
authors: Zhang
authors: Zhenwei
authors: Z
authors: Xia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000096:biosynthesis* / Q000097:blood; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D006932:Hyperbilirubinemia / Q000201:enzymology* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019076:Transgenes
chemical_list: D034741:RNA, Small Interfering; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D001663:Bilirubin