Cardioprotection with α-tocopheryl phosphate

Amelioration of myocardial ischemia reperfusion injury is linked with its ability to generate a survival signal through Akt activation

Subhendu Mukherjee, I. Lekli, Manika Das, Angelo Azzi, Dipak K. Das

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The emerging potential of α-tocopheryl phosphate, a phosphoric acid ester of α-tocopherol, in health benefits was tested gavaging this compound (5 mg/kg body wt) to a group of rats for a period of thirty days while the control rats were given water only. After thirty days, the rats were sacrificed, the hearts excised, and the isolated hearts were perfused by working mode. Both control and experimental hearts were subjected to 30-min global ischemia followed by 2 h of reperfusion. The tocopheryl phosphate fed rats exhibited significant cardioprotection as evidenced by improved ventricular performance and reduced myocardial infarct size and cardiomyocyte apoptosis. Supplementation with α-tocopheryl phosphate converted MAP kinase-induced death signal into a survival signal by enhancing anti-apoptotic p42/44 ERK kinase and p38 MAPKβ and reducing pro-apoptotic proteins p38 MAPKα and JNK. In concert, the phosphorylation of pro-apoptotic c-Src was also reduced. Tocopheryl phosphate increased the DNA binding of the redox-sensitive transcription factor NFκB and potentiated the activation of anti-death protein Bcl-2 and survival signaling protein Akt. The results of this study demonstrated for the first time that tocopheryl phosphate could ameliorate myocardial ischemic reperfusion injury by converting ischemia/reperfusion-mediated death signal into a survival signal by modulating MAP kinase signaling.

Original languageEnglish
Pages (from-to)498-503
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1782
Issue number9
DOIs
Publication statusPublished - Sep 2008

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Myocardial Reperfusion Injury
Reperfusion Injury
Myocardial Ischemia
Phosphotransferases
p38 Mitogen-Activated Protein Kinases
Reperfusion
Ischemia
Apoptosis Regulatory Proteins
Tocopherols
Organophosphates
Insurance Benefits
Cardiac Myocytes
Oxidation-Reduction
Proteins
Transcription Factors
Myocardial Infarction
Phosphorylation
alpha-tocopherol phosphate
Apoptosis
Water

Keywords

  • α-Tocotrienol
  • Akt
  • c-Src
  • Cardioprotection
  • Ischemia reperfusion injury
  • MAP kinase
  • Tocopheryl phosphate

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

Cite this

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title = "Cardioprotection with α-tocopheryl phosphate: Amelioration of myocardial ischemia reperfusion injury is linked with its ability to generate a survival signal through Akt activation",
abstract = "The emerging potential of α-tocopheryl phosphate, a phosphoric acid ester of α-tocopherol, in health benefits was tested gavaging this compound (5 mg/kg body wt) to a group of rats for a period of thirty days while the control rats were given water only. After thirty days, the rats were sacrificed, the hearts excised, and the isolated hearts were perfused by working mode. Both control and experimental hearts were subjected to 30-min global ischemia followed by 2 h of reperfusion. The tocopheryl phosphate fed rats exhibited significant cardioprotection as evidenced by improved ventricular performance and reduced myocardial infarct size and cardiomyocyte apoptosis. Supplementation with α-tocopheryl phosphate converted MAP kinase-induced death signal into a survival signal by enhancing anti-apoptotic p42/44 ERK kinase and p38 MAPKβ and reducing pro-apoptotic proteins p38 MAPKα and JNK. In concert, the phosphorylation of pro-apoptotic c-Src was also reduced. Tocopheryl phosphate increased the DNA binding of the redox-sensitive transcription factor NFκB and potentiated the activation of anti-death protein Bcl-2 and survival signaling protein Akt. The results of this study demonstrated for the first time that tocopheryl phosphate could ameliorate myocardial ischemic reperfusion injury by converting ischemia/reperfusion-mediated death signal into a survival signal by modulating MAP kinase signaling.",
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AU - Das, Manika

AU - Azzi, Angelo

AU - Das, Dipak K.

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