Peroxisome proliferator-activated receptor alpha plays a crucial role in L-carnitine anti-apoptosis effect in renal tubular cells.

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TMUIR > Wan Fang Hospital, Taipei Medical University > Department of Internal Medicine > Periodical Articles > Item 987654321/44261

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Title:	Peroxisome proliferator-activated receptor alpha plays a crucial role in L-carnitine anti-apoptosis effect in renal tubular cells.
Authors:	Chen HH;Sue YM;Chen CH;Hsu YH;Hou CC;Cheng CY;Lin SL;Tsai WL;Chen TW;Chen TH.
Date:	2009
Issue Date:	2011-08-30 14:23:54 (UTC+8)
Abstract:	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.
Relation:	Nephrol Dial Transplant. 2009 Oct;24(10):3042-9. Epub 2009 Jun 2.
Appears in Collections:	[Department of Internal Medicine] Periodical Articles

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