Functional modulation of mitochondria by eicosapentaenoic acid provides protection against ceramide toxicity to C6 glioma cells

Jaa Yeh Jeng, Wei Hwa Lee, Ya-Hui Tsai, Chia Yu Chen, Szu Yi Chao, Rong Hong Hsieh

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mitochondrial dysfunction and associated apoptosis have been reported in the pathogenesis of neuron degeneration. The effects of eicosapentaenoic acid (EPA) and arachidonic acid (AA) on the mitochondrial membrane potential, mitochondrial biogenesis, and mitochondrial function of rat C6 glioma cells were determined in this study. Increased cytochrome c release and activated caspase-3 expression were determined in cells treated with >20 μM C 2 ceramide. There were significant repressive effects on ceramide-induced cell death with 25-100 μM EPA and 25 μM AA pretreatment. However, significantly increased membrane potentials were detected in cells pretreated with 25 and 50 μM EPA compared to ceramide-treated cells, but not in AA pretreatment groups. In cells pretreated with EPA, ATP production loss was prevented from ceramide-induced mitochondrial dysfunction. In mitochondrial biogenesis related assay, both EPA and AA enhanced peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α) and mitochondrial transcription factor A (Tfam) transcriptional activities. However, elevated PGC-1α transcriptional activities in groups pretreated with 25, 50, and 100 μM EPA and only in the 100 μM AA group were analyzed. The Tfam transcriptional activities were enhanced in groups pretreated with 25 and 50 μM EPA and AA. Increased NADH dehydrogenase subunit 6 (ND6) mRNA expression was determined in cells pretreated with 25 and 50 μM EPA and 25 μM AA. Elevated protein levels of Tfam, flavoprotein, and cytochrome oxidase subunit III (COX III) were determined in cells pretreated with 25 and 50 μM EPA. The EPA-provided a more protective effect than AA against ceramide-induced cell death, which might mainly be due to maintaining the membrane potential and sustaining the mitochondrial ATP production function. EPA has more potential to elevate mitochondrial biogenesis through enhanced PGC-1α, and Tfam transcriptional activities may provide partial protection against ceramide cytotoxicity.

Original languageEnglish
Pages (from-to)11455-11462
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume57
Issue number24
DOIs
Publication statusPublished - Dec 23 2009

Fingerprint

ceramides
Mitochondria
Eicosapentaenoic Acid
Ceramides
eicosapentaenoic acid
Glioma
Toxicity
mitochondria
Modulation
arachidonic acid
Arachidonic Acid
toxicity
cells
Organelle Biogenesis
membrane potential
Mitochondrial Membrane Potential
Cell death
Membranes
cell death
Cell Death

Keywords

  • Arachidonic acid
  • Ceramide
  • Eicosapentaenoic acid
  • Mitochondrial biogenesis
  • Mitochondrial transcription factor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Chemistry(all)

Cite this

Functional modulation of mitochondria by eicosapentaenoic acid provides protection against ceramide toxicity to C6 glioma cells. / Jeng, Jaa Yeh; Lee, Wei Hwa; Tsai, Ya-Hui; Chen, Chia Yu; Chao, Szu Yi; Hsieh, Rong Hong.

In: Journal of Agricultural and Food Chemistry, Vol. 57, No. 24, 23.12.2009, p. 11455-11462.

Research output: Contribution to journalArticle

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abstract = "Mitochondrial dysfunction and associated apoptosis have been reported in the pathogenesis of neuron degeneration. The effects of eicosapentaenoic acid (EPA) and arachidonic acid (AA) on the mitochondrial membrane potential, mitochondrial biogenesis, and mitochondrial function of rat C6 glioma cells were determined in this study. Increased cytochrome c release and activated caspase-3 expression were determined in cells treated with >20 μM C 2 ceramide. There were significant repressive effects on ceramide-induced cell death with 25-100 μM EPA and 25 μM AA pretreatment. However, significantly increased membrane potentials were detected in cells pretreated with 25 and 50 μM EPA compared to ceramide-treated cells, but not in AA pretreatment groups. In cells pretreated with EPA, ATP production loss was prevented from ceramide-induced mitochondrial dysfunction. In mitochondrial biogenesis related assay, both EPA and AA enhanced peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α) and mitochondrial transcription factor A (Tfam) transcriptional activities. However, elevated PGC-1α transcriptional activities in groups pretreated with 25, 50, and 100 μM EPA and only in the 100 μM AA group were analyzed. The Tfam transcriptional activities were enhanced in groups pretreated with 25 and 50 μM EPA and AA. Increased NADH dehydrogenase subunit 6 (ND6) mRNA expression was determined in cells pretreated with 25 and 50 μM EPA and 25 μM AA. Elevated protein levels of Tfam, flavoprotein, and cytochrome oxidase subunit III (COX III) were determined in cells pretreated with 25 and 50 μM EPA. The EPA-provided a more protective effect than AA against ceramide-induced cell death, which might mainly be due to maintaining the membrane potential and sustaining the mitochondrial ATP production function. EPA has more potential to elevate mitochondrial biogenesis through enhanced PGC-1α, and Tfam transcriptional activities may provide partial protection against ceramide cytotoxicity.",
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