| Sue YM |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.167 ------>paper_class3=2 ------>paper_class2=1 ------>vol=24 ------>confirm_bywho=ncchang ------>insert_bywho=sueym ------>Jurnal_Rank=20.0 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=777 ------>medlineContent= ------>unit=E0109 ------>insert_date=20081124 ------>iam=1 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=0931-0509 ------>authors_c= ------>score=500 ------>journal_name=Nephrology Dialysis Transplantation ------>paper_name=Antioxidation and anti-inflammation by haem oxygenase-1 contribute to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells ------>confirm_date=20090306 ------>tch_id=093141 ------>pmid=18842672 ------>page1=769 ------>fullAbstract=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-kappaB-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-kappaB-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 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 gentamicin-induced nephrotoxicity through antiapoptotic and anti-inflammatory mechanisms, and that it may have therapeutic potential for patients with renal disease. This is also the first demonstration that HO-1 increases Hax-1 mitochondrial localization. ------>tmu_sno=None ------>sno=19817 ------>authors2=Cheng CF ------>authors3=Chang CC ------>authors4=Chou Y ------>authors5=Chen CH ------>authors6=Juan SH ------>authors6_c= ------>authors=Sue YM ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Antioxidation and anti-inflammation by haem oxygenase-1 contribute to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=3 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=3 |