IR@PKUHSC  > 北京大学第一临床医学院  > 肾脏内科
学科主题临床医学
Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production
Zhang, Yanling; Wada, Jun; Hashimoto, Izumi; Eguchi, Jun; Yasuhara, Akihiro; Kanwar, Yashpal S.; Shikata, Kenichi; Makino, Hirofumi
刊名JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2006-04-01
DOI10.1681/ASN.2005111148
17期:4页:1090-1101
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Urology & Nephrology
研究领域[WOS]Urology & Nephrology
关键词[WOS]PROXIMAL TUBULE CELLS ; PROTEIN IMPORT ; OXIDATIVE STRESS ; RENAL-FAILURE ; MEMBRANE ; PREPROTEINS ; CULTURE ; RATS ; COMPLICATIONS ; RECEPTORS
英文摘要

Hyperglycemia-induced overproduction of mitochondrial reactive oxygen species has emerged as a major player in diabetic vascular complications. Mammalian translocase of inner mitochondrial membrane 44 (TIM44) was identified by upregulation in diabetic mouse kidneys. TIM44 functions as a membrane anchor of mitochondrial heat-shock protein 70 (mtHsp70) to TIM23 complex and is involved in the import of mitochondria-targeted preproteins into mitochondrial matrix. The process is dependent on inner membrane potential and ATP hydrolysis on ATPase domain of mitochondrial heat-shock protein 70. Hemagglutination virus of Japan-envelope vector that carries pcDNA3.1 plasmid that contains the full-length cDNA of TIM44 and control plasmid were injected weekly into the tail vein of uninephrectomized streptozotocin-induced diabetic CD-1 mice. The gene delivery alleviated proteinuria and renal hypertrophy at 8 wk after the injection, inhibited renal cell proliferation and apoptosis, and suppressed superoxide production. In vitro experiments, using human proximal tubular (HK2) cells, revealed that the gene delivery of TIM44 reversed high glucose-induced metabolic and cellular abnormalities such as enhanced reactive oxygen species production, increased ATP contents, alterations in inner membrane potential, increased cell proliferation, and apoptosis. Transfection with siRNA and expressing vector of TIM44 revealed that TIM44 facilitates import of antioxidative enzymes such as superoxide dismutase and glutathione peroxidase into mitochondria. The gene delivery of TIM44 therefore seems to be beneficial for the maintenance of mitochondrial function and is a novel therapeutic approach for diabetic nephropathy.

语种英语
WOS记录号WOS:000242120600023
Citation statistics
Cited Times:49[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56077
Collection北京大学第一临床医学院_肾脏内科
作者单位1.Okayama Univ, Grad Sch Med, Dept Med & Clin Sci, Okayama 7008558, Japan
2.Peking Univ, Hosp 1, Div Renal, Inst Nephrol, Beijing 100871, Peoples R China
3.Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA
Recommended Citation
GB/T 7714
Zhang, Yanling,Wada, Jun,Hashimoto, Izumi,et al. Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production[J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY,2006,17(4):1090-1101.
APA Zhang, Yanling.,Wada, Jun.,Hashimoto, Izumi.,Eguchi, Jun.,Yasuhara, Akihiro.,...&Makino, Hirofumi.(2006).Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production.JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY,17(4),1090-1101.
MLA Zhang, Yanling,et al."Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production".JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 17.4(2006):1090-1101.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
谷歌学术
谷歌学术Similar articles in
[Zhang, Yanling]'s Articles
[Wada, Jun]'s Articles
[Hashimoto, Izumi]'s Articles
百度学术
百度学术Similar articles in
[Zhang, Yanling]'s Articles
[Wada, Jun]'s Articles
[Hashimoto, Izumi]'s Articles
必应学术
必应学术Similar articles in
[Zhang, Yanling]'s Articles
[Wada, Jun]'s Articles
[Hashimoto, Izumi]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.