Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats

	Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats
	Li, W; Zhu, LH; Wang, EB; Ye, ZC; Lin, J; Guo, LH; Luo, FH; Liu, XH; Fang, X; Shen, SX
刊名	ACTA PHARMACOLOGICA SINICA
	2004
卷号	25 期号:4 页码:490-495
关键词	growth hormone diabetic nephropathies mutation diabetes mellitus
通讯作者	Guo, LH (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,lhguo@sunm.shcnc.ac.cn
英文摘要	AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-dell-4, G120R, K168A, E174A, C182S, del186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC(50) (Mean +/- SD) values for the mutants for inhibiting (121)I-hGH binding to rabbit growth hormone receptor were (65 +/- 10) ng for hGHA1, (27 +/- 5.6) ng for hGHA2, and (10 +/- 0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.
学科主题	Chemistry; Pharmacology & Pharmacy
类目[WOS]	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
关键词[WOS]	TRANSGENIC MICE ; EXTRACELLULAR DOMAIN ; RATIONAL DESIGN ; GH ANTAGONIST ; DIMERIZATION ; NEPHROPATHY
收录类别	SCI
语种	英语
WOS记录号	WOS:000220750000016
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2076]
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	Li, W,Zhu, LH,Wang, EB,et al. Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats[J]. ACTA PHARMACOLOGICA SINICA,2004,25(4):490-495.
APA	Li, W.,Zhu, LH.,Wang, EB.,Ye, ZC.,Lin, J.,...&Shen, SX.(2004).Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats.ACTA PHARMACOLOGICA SINICA,25(4),490-495.
MLA	Li, W,et al."Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats".ACTA PHARMACOLOGICA SINICA 25.4(2004):490-495.