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 (PGI2) generation in NRK-52E cells. The siRNA transfection for PGI2 synthase significantly reduced l-carnitine-induced PGI2 and l-carnitine's protective effect. We found that the activity of the potential PGI2 nuclear receptor, peroxisome proliferator-activated receptor alpha (PPARα), was elevated by l-carnitine treatment. The siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of l-carnitine. In PPARα-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 PGI2-mediated PPARα activation.

Original languageEnglish
Pages (from-to)3042-3049
Number of pages8
JournalNephrology Dialysis Transplantation
Volume24
Issue number10
DOIs
Publication statusPublished - Oct 2009

Fingerprint

PPAR alpha
Carnitine
Apoptosis
Kidney
Gentamicins
Epoprostenol
Small Interfering RNA
Transfection
Epoprostenol Receptors
DNA Nucleotidylexotransferase
Poisons
Cytoplasmic and Nuclear Receptors
Methionine
Antineoplastic Agents
Lysine
Reactive Oxygen Species

Keywords

  • Apoptosis
  • Gentamicin
  • L-carnitine
  • Peroxisome proliferator-activated receptor alpha (PPARα)
  • Prostacyclin (PGI 2)

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

@article{afcd5a1d515c448aa24a1333c2325f2c,
title = "Peroxisome proliferator-activated receptor alpha plays a crucial role in l-carnitine anti-apoptosis effect in renal tubular cells",
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 (PGI2) generation in NRK-52E cells. The siRNA transfection for PGI2 synthase significantly reduced l-carnitine-induced PGI2 and l-carnitine's protective effect. We found that the activity of the potential PGI2 nuclear receptor, peroxisome proliferator-activated receptor alpha (PPARα), was elevated by l-carnitine treatment. The siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of l-carnitine. In PPARα-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 PGI2-mediated PPARα activation.",
keywords = "Apoptosis, Gentamicin, L-carnitine, Peroxisome proliferator-activated receptor alpha (PPARα), Prostacyclin (PGI 2)",
author = "Chen, {Hsi Hsien} and Sue, {Yuh Mou} and Chen, {Cheng Hsien} and Hsu, {Yung Ho} and Chun-Cheng Hou and Cheng, {Chung Yi} and Lin, {Shih Li} and Tsai, {Wei Lun} and Tzen-Wen Chen and Chen, {Tso Hsiao}",
year = "2009",
month = "10",
doi = "10.1093/ndt/gfp258",
language = "English",
volume = "24",
pages = "3042--3049",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Peroxisome proliferator-activated receptor alpha plays a crucial role in l-carnitine anti-apoptosis effect in renal tubular cells

AU - Chen, Hsi Hsien

AU - Sue, Yuh Mou

AU - Chen, Cheng Hsien

AU - Hsu, Yung Ho

AU - Hou, Chun-Cheng

AU - Cheng, Chung Yi

AU - Lin, Shih Li

AU - Tsai, Wei Lun

AU - Chen, Tzen-Wen

AU - Chen, Tso Hsiao

PY - 2009/10

Y1 - 2009/10

N2 - 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 (PGI2) generation in NRK-52E cells. The siRNA transfection for PGI2 synthase significantly reduced l-carnitine-induced PGI2 and l-carnitine's protective effect. We found that the activity of the potential PGI2 nuclear receptor, peroxisome proliferator-activated receptor alpha (PPARα), was elevated by l-carnitine treatment. The siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of l-carnitine. In PPARα-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 PGI2-mediated PPARα activation.

AB - 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 (PGI2) generation in NRK-52E cells. The siRNA transfection for PGI2 synthase significantly reduced l-carnitine-induced PGI2 and l-carnitine's protective effect. We found that the activity of the potential PGI2 nuclear receptor, peroxisome proliferator-activated receptor alpha (PPARα), was elevated by l-carnitine treatment. The siRNA-mediated blockage of PPARα considerably reduced the anti-apoptotic effect of l-carnitine. In PPARα-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 PGI2-mediated PPARα activation.

KW - Apoptosis

KW - Gentamicin

KW - L-carnitine

KW - Peroxisome proliferator-activated receptor alpha (PPARα)

KW - Prostacyclin (PGI 2)

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U2 - 10.1093/ndt/gfp258

DO - 10.1093/ndt/gfp258

M3 - Article

VL - 24

SP - 3042

EP - 3049

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 10

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