Abstract

To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-α (PPARα), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARα short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARα activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARα knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARα-signaling pathway.

Original languageEnglish
Pages (from-to)578-587
Number of pages10
JournalKidney International
Volume73
Issue number5
DOIs
Publication statusPublished - Mar 2008

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Peroxisome Proliferator-Activated Receptors
Epoprostenol
Gentamicins
Apoptosis
Kidney
Caspase 3
Cyclooxygenase 1
Caspase 9
Docosahexaenoic Acids
Cytoplasmic and Nuclear Receptors
Cytochromes c
Adenoviridae
Knockout Mice
Small Interfering RNA
Reactive Oxygen Species
Cell Count

Keywords

  • Docosahexaenoic acid (DHA)
  • Gentamicin
  • Peroxisome proliferator-activated receptor alpha (PPARα)
  • Prostacyclin (PGI)
  • Renal tubular cell

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Prostacyclin protects renal tubular cells from gentamicin-induced apoptosis via a PPARα-dependent pathway",
abstract = "To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-α (PPARα), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARα short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARα activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARα knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARα-signaling pathway.",
keywords = "Docosahexaenoic acid (DHA), Gentamicin, Peroxisome proliferator-activated receptor alpha (PPARα), Prostacyclin (PGI), Renal tubular cell",
author = "Hsu, {Y. H.} and Chen, {C. H.} and Hou, {C. C.} and Sue, {Y. M.} and Cheng, {C. Y.} and Cheng, {T. H.} and H. Lin and Tsai, {W. L.} and P. Chan and Chen, {T. H.}",
year = "2008",
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T1 - Prostacyclin protects renal tubular cells from gentamicin-induced apoptosis via a PPARα-dependent pathway

AU - Hsu, Y. H.

AU - Chen, C. H.

AU - Hou, C. C.

AU - Sue, Y. M.

AU - Cheng, C. Y.

AU - Cheng, T. H.

AU - Lin, H.

AU - Tsai, W. L.

AU - Chan, P.

AU - Chen, T. H.

PY - 2008/3

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N2 - To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-α (PPARα), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARα short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARα activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARα knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARα-signaling pathway.

AB - To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-α (PPARα), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARα short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARα activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARα knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARα-signaling pathway.

KW - Docosahexaenoic acid (DHA)

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