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Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.
- Source :
-
Experimental biology and medicine (Maywood, N.J.) [Exp Biol Med (Maywood)] 2007 Apr; Vol. 232 (4), pp. 495-502. - Publication Year :
- 2007
-
Abstract
- Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage.
- Subjects :
- Cell Line
Heme Oxygenase-1 genetics
Hemin pharmacology
Humans
Hyperbilirubinemia, Neonatal drug therapy
Hyperbilirubinemia, Neonatal genetics
Kernicterus drug therapy
Kernicterus genetics
Liver enzymology
Oxidation-Reduction
Up-Regulation
Bilirubin metabolism
Gene Expression Regulation, Enzymologic
Heme Oxygenase-1 metabolism
Hyperbilirubinemia, Neonatal enzymology
Kernicterus enzymology
RNA, Small Interfering genetics
RNA, Small Interfering therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3702
- Volume :
- 232
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Experimental biology and medicine (Maywood, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 17392485