Chen HH |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.568 ------>paper_class3=2 ------>paper_class2=1 ------>vol=24 ------>confirm_bywho=None ------>insert_bywho=sueym ------>Jurnal_Rank=19.3 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=3049 ------>medlineContent= ------>unit=E0109 ------>insert_date=20091012 ------>iam=2 ------>update_date=None ------>author=??? ------>change_event=1 ------>ISSN=0931-0509 ------>authors_c= ------>score=500 ------>journal_name=Nephrol Dial Transplant ------>paper_name=Peroxisome proliferator-activated receptor alpha plays a crucial role in L-carnitine anti-apoptosis effect in renal tubular cells. ------>confirm_date=None ------>tch_id=093141 ------>pmid=19491382 ------>page1=3042 ------>fullAbstract=BACKGROUND: L-carnitine is synthesized mainly in the liver and kidneys from lysine and methionine from dietary sources. Many reports have shown that L-carnitine can protect certain cells against the toxicity of several anticancer and toxic agents, although the detailed mechanism is poorly understood. In this study, we investigated the protective effect of L-carnitine and its molecular mechanism in renal tubular cells undergoing gentamicin-induced apoptosis. METHODS: Rat tubular cell line (NRK-52E) and mice were used as the model system. Gentamicin-induced apoptosis in renal tubular cells was examined using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling. We introduced short interfering RNA transfection and gene-deficient mice to investigate the protective mechanism of L-carnitine. RESULTS: We found that L-carnitine inhibited gentamicin-induced reactive oxygen species generation and correlative apoptotic pathways, resulting in the protection of NRK-52E cells from gentamicin-induced apoptosis. The treatment of L-carnitine also lessened gentamicin-induced renal tubular cell apoptosis in mice. L-carnitine was found to increase the prostacyclin (PGI(2)) generation in NRK-52E cells. The siRNA transfection for PGI(2) synthase significantly reduced L-carnitine-induced PGI(2) and L-carnitine~s protective effect. We found that the activity of the potential PGI(2) nuclear receptor, peroxisome proliferator-activated receptor alpha (PPARalpha), was elevated by L-carnitine treatment. The siRNA-mediated blockage of PPARalpha considerably reduced the anti-apoptotic effect of L-carnitine. In PPARalpha-deficient mice, L-carnitine treatment also lost the inhibitory effect on gentamicin-induced apoptosis in kidneys. CONCLUSIONS: Based on these findings, we suggest that L-carnitine protects renal tubular cells from gentamicin-induced apoptosis through PGI(2)-mediated PPARalpha activation. ------>tmu_sno=None ------>sno=22481 ------>authors2=Sue YM ------>authors3=Chen CH ------>authors4=Hsu YH ------>authors5=Hou CC ------>authors6=Cheng CY, Lin SL, Tsai WL, Chen TW, Chen TH ------>authors6_c= ------>authors=Chen HH ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Peroxisome proliferator-activated receptor alpha plays a crucial role in L-carnitine anti-apoptosis effect in renal tubular cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=10 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=10 |