Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA

	Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA
	Xia, ZW; Li, CE; Jin, Y; Shi, Y; Xu, LQ; Zhong, WW; Li, YZ; Yu, SC; Zhang, ZL
刊名	EXPERIMENTAL BIOLOGY AND MEDICINE
	2007
卷号	232 期号:4 页码:495-502
关键词	heme oxygenase RNA-mediated interference small interfering RNA bilirubin hyperbilirubinemia
通讯作者	Xia, ZW (reprint author), Shanghai Jiao Tong Univ, Dept Pediat, Ruijin Hosp, Sch Med, Ruijin 2nd,Rd 197, Shanghai 200025, Peoples R China.,xzw63@hotmail.com
英文摘要	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.
学科主题	Research & Experimental Medicine
类目[WOS]	Medicine, Research & Experimental
关键词[WOS]	NEONATAL JAUNDICE ; RNA INTERFERENCE ; HYPERBILIRUBINEMIA ; NEWBORNS ; INFANTS ; TRIGGER ; EVENTS
收录类别	SCI
语种	英语
WOS记录号	WOS:000245322900005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1555]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xia, ZW,Li, CE,Jin, Y,et al. Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA[J]. EXPERIMENTAL BIOLOGY AND MEDICINE,2007,232(4):495-502.
APA	Xia, ZW.,Li, CE.,Jin, Y.,Shi, Y.,Xu, LQ.,...&Zhang, ZL.(2007).Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.EXPERIMENTAL BIOLOGY AND MEDICINE,232(4),495-502.
MLA	Xia, ZW,et al."Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA".EXPERIMENTAL BIOLOGY AND MEDICINE 232.4(2007):495-502.