Pyruvate dehydrogenase alpha 1 as a target of omega-3 polyunsaturated fatty acids in human prostate cancer through a global phosphoproteomic analysis

Heng Zhao, Beth Pflug, Xianyin Lai, Mu Wang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Prostate cancer is one of the leading cancers in men. Taking dietary supplements, such as fish oil (FO), which is rich in n-3 polyunsaturated fatty acids (PUFAs), has been employed as a strategy to lower prostate cancer risk and control disease progression. In this study, we investigated the global phosphoproteomic changes induced by FO using a combination of phosphoprotein-enrichment strategy and high-resolution tandem mass spectrometry. We found that FO induces many more phosphorylation changes than oleic acid when they both are compared to control group. Quantitative comparison between untreated group and FO- or oleic acid-treated groups uncovered a number of important protein phosphorylation changes induced by n-3PUFAs. This phosphoproteomic discovery study and the follow-up Western Blot validation study elucidate that phosphorylation levels of the two regulatory serine residues in pyruvate dehydrogenase alpha 1 (PDHA1), serine-232 and serine-300, are significantly decreased upon FO treatment. As expected, increased pyruvate dehydrogenase activity was also observed. This study suggests that FO-induced phosphorylation changes in PDHA1 is more likely related to the glucose metabolism pathway, and n-3 PUFAs may have a role in controlling the balance between lipid and glucose oxidation.

Original languageEnglish (US)
Pages (from-to)2419-2431
Number of pages13
JournalProteomics
Volume16
Issue number17
DOIs
StatePublished - Sep 1 2016

Fingerprint

Fish Oils
Omega-3 Fatty Acids
Pyruvic Acid
Unsaturated Fatty Acids
Prostatic Neoplasms
Oxidoreductases
Phosphorylation
Serine
Oleic Acid
Dietary supplements
Disease control
Glucose
Validation Studies
Phosphoproteins
Dietary Supplements
Tandem Mass Spectrometry
Metabolism
Mass spectrometry
Disease Progression
Western Blotting

Keywords

  • Biomedicine
  • Fish oil
  • Phosphoproteomics
  • Prostate cancer
  • Pyruvate dehydrogenase
  • Unsaturated fatty acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Pyruvate dehydrogenase alpha 1 as a target of omega-3 polyunsaturated fatty acids in human prostate cancer through a global phosphoproteomic analysis. / Zhao, Heng; Pflug, Beth; Lai, Xianyin; Wang, Mu.

In: Proteomics, Vol. 16, No. 17, 01.09.2016, p. 2419-2431.

Research output: Contribution to journalArticle

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