Antioxidation and anti-inflammation by heme oxygenase-1 contributes to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells

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题名:	Antioxidation and anti-inflammation by heme oxygenase-1 contributes to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells
作者:	阮淑慧 Sue YM;Cheng CF;Chang CC;Chau Y;Chen CH;Juan SH
贡献者:	醫學系生理學科
日期:	2009
上传时间:	2009-08-24 10:44:25 (UTC+8)
摘要:	Background. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. Tetramethylpyrazine (TMP) is a compound purified from the rhizome of Ligusticum wallichi (called chuanxiong in Chinese). Besides its protection against ischaemia– reperfusion injury and nephritis in mice, we previously reported that TMP reverses gentamicin-induced apoptosis in rat kidneys. Haem oxygenase-1 (HO-1) induction by TMP has also been shown to attenuate myocardial ischaemia/ reperfusion injury in rats. Methods.We used rat renal tubular (NRK-52E) cells, transformed cells with HO-1 overexpression or knockdown, and an adenovirus carrying the HO-1 gene (Adv-HO-1) as gene therapy targeting murine kidneys to explore the role of HO- 1 in protection by TMP against gentamicin-induced toxicity both in vitro and in vivo. We evaluated the protective effects of HO-1 on several apoptotic parameters induced by gentamicin: cleaved caspases-3 and -9, cycloxygenase-2 (Cox-2) and subcellular localization of nuclear factor kappa B-p65 (NF-κB-p65), Bcl-xl and HS-1-associated protein (Hax-1) in NRK-52E cells. Results. NRK-52E cells treated with TMP exhibited transcriptional upregulation of the HO-1 protein by approximately twofold. Overexpression of HO-1 in NRK-52E cells significantly increased mitochondrial protein levels of the antiapoptotic molecules, Bcl-xL and Hax-1, and markedly decreased the NADPH oxidase activity and proinflammatory molecules, NF-κB-p65 and Cox-2, which might decrease gentamicin-induced activation of caspases-9 and -3. Conversely, NRK-52E cells with HO-1 knockdown significantly exacerbated gentamicin-induced tubular cell apoptosis. Additionally, the concomitant HO-1 induction by TMP Correspondence and offprint requests to: Shu-Hui Juan, Department of Physiology, Graduate Institute of Medical Sciences and Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan. Tel: +886-2-27361661; Ext. 3178; Fax: +886-2-23461737; E-mail: [email protected] was also evident in vivo, and HO-1 therapy markedly attenuated gentamicin-induced renal apoptosis to a similar extent as TMP pretreatment. Conclusions. Collectively, we suggest that HO-1 induced by TMP might, at least in part, protect against gentamicininduced nephrotoxicity through antiapoptotic and antiinflammatory mechanisms, and that it may have therapeutic potential for patientswith renal disease. This is also the first demonstration that HO-1 increases Hax-1 mitochondrial localization. Keywords: apoptosis; haem oxygenase; HS-1-associated protein (HAX-1); NADPH oxidase; tetramethylpyrazine (TMP)
關聯:	Nephrology Dialysis Transplantation.(24):769-77.
数据类型:	article
显示于类别:	[生理學科] 期刊論文

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