Targeted suppression of heme oxygenase-1 by small interference RNAs inhibits the production of bilirubin in neonatal rat with hyperbilirubinemia.

Authors: Wu, J  Su, W  Jin, Y  Shi, Y  Li, C  Zhong, W  Zhang, X  Zhang, Z  Xia, Z 
Citation: Wu J, etal., BMC Mol Biol. 2009 Aug 1;10:77.
Pubmed: (View Article at PubMed) PMID:19646271
DOI: Full-text: DOI:10.1186/1471-2199-10-77

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. CONCLUSION: 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.

Annotation

Disease Annotations
RGD Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 4145302
Created: 2010-10-29
Species: All species
Last Modified: 2010-10-29
Status: ACTIVE