Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 and C-JUN

Motoaki Sato, Debasis Bagchi, A. Tósaki, Dipak K. Das

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

The mechanism of cardioprotection with red wine consumption was studied by examining the antideath signaling cascade of one of the principle components of red wine, proanthocyanidins. Grape seed proanthocyanidin extract (GSPE) was administered orally (100 mg/kg/d) supplemented with regular diet for 3 weeks to a group of rats while the other group was given the regular diet only for the same period of time. After 3 weeks, rats were sacrificed, hearts excised, and perfused via Langendorff mode. After stabilization, hearts were perfused in the working mode for baseline measurement of contractile function. Hearts were then made globally ischemic for 30 min followed by 2 h of reperfusion. Contratile function was continuously monitored during reperfusion, and free radical production was examined by electron spin resonance (ESR) technique. Cardiomyocyte apoptosis was examined by TUNEL staining in conjunction with an antibody against myocin heavy chain to specifically detect myocytes. Induction of JNK-1 and c-fos proteins was studied by Western blot analysis using respective antibodies followed by densitometric scanning. The results indicated significant induction of JNK-1 and c-fos proteins in the ischemic/reperfused myocardium, which was inhibited by the proanthocyanidin extract. In concert, GSPE significantly reduced the appearance of apoptotic cardiomyocytes in the ischemic/reperfused hearts. GSPE also significantly reduced the appearance of the reactive oxygen species in the hearts. Improved postischemic contractile recovery was achieved with GSPE suggesting its cardioprotective action. The results of this study indicated that GSPE functioned as an in vivo antioxidant, and its cardioprotective properties may be at least partially attributed to its ability to block antideath signal through the inhibition of proapoptotic transcription factor and gene, JNK-1 and c-Jun.

Original languageEnglish
Pages (from-to)729-737
Number of pages9
JournalFree Radical Biology and Medicine
Volume31
Issue number6
DOIs
Publication statusPublished - Sep 15 2001

Fingerprint

Grape Seed Extract
Cardiac Myocytes
Reperfusion
Ischemia
Chemical activation
Apoptosis
Proto-Oncogene Proteins c-fos
Wine
Nutrition
Rats
Diet
Proanthocyanidins
Antibodies
In Situ Nick-End Labeling
Electron Spin Resonance Spectroscopy
Muscle Cells
Free Radicals
Paramagnetic resonance
Reactive Oxygen Species
Myocardium

Keywords

  • Alcohol
  • Apoptosis
  • C-Jun
  • Cardiomyocytes
  • Free radicals
  • Heart
  • JNK
  • Proanthocyanidins
  • Wine

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 and C-JUN. / Sato, Motoaki; Bagchi, Debasis; Tósaki, A.; Das, Dipak K.

In: Free Radical Biology and Medicine, Vol. 31, No. 6, 15.09.2001, p. 729-737.

Research output: Contribution to journalArticle

@article{165859f03eed4cc8b3c86b7112ba3525,
title = "Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 and C-JUN",
abstract = "The mechanism of cardioprotection with red wine consumption was studied by examining the antideath signaling cascade of one of the principle components of red wine, proanthocyanidins. Grape seed proanthocyanidin extract (GSPE) was administered orally (100 mg/kg/d) supplemented with regular diet for 3 weeks to a group of rats while the other group was given the regular diet only for the same period of time. After 3 weeks, rats were sacrificed, hearts excised, and perfused via Langendorff mode. After stabilization, hearts were perfused in the working mode for baseline measurement of contractile function. Hearts were then made globally ischemic for 30 min followed by 2 h of reperfusion. Contratile function was continuously monitored during reperfusion, and free radical production was examined by electron spin resonance (ESR) technique. Cardiomyocyte apoptosis was examined by TUNEL staining in conjunction with an antibody against myocin heavy chain to specifically detect myocytes. Induction of JNK-1 and c-fos proteins was studied by Western blot analysis using respective antibodies followed by densitometric scanning. The results indicated significant induction of JNK-1 and c-fos proteins in the ischemic/reperfused myocardium, which was inhibited by the proanthocyanidin extract. In concert, GSPE significantly reduced the appearance of apoptotic cardiomyocytes in the ischemic/reperfused hearts. GSPE also significantly reduced the appearance of the reactive oxygen species in the hearts. Improved postischemic contractile recovery was achieved with GSPE suggesting its cardioprotective action. The results of this study indicated that GSPE functioned as an in vivo antioxidant, and its cardioprotective properties may be at least partially attributed to its ability to block antideath signal through the inhibition of proapoptotic transcription factor and gene, JNK-1 and c-Jun.",
keywords = "Alcohol, Apoptosis, C-Jun, Cardiomyocytes, Free radicals, Heart, JNK, Proanthocyanidins, Wine",
author = "Motoaki Sato and Debasis Bagchi and A. T{\'o}saki and Das, {Dipak K.}",
year = "2001",
month = "9",
day = "15",
doi = "10.1016/S0891-5849(01)00626-8",
language = "English",
volume = "31",
pages = "729--737",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Grape seed proanthocyanidin reduces cardiomyocyte apoptosis by inhibiting ischemia/reperfusion-induced activation of JNK-1 and C-JUN

AU - Sato, Motoaki

AU - Bagchi, Debasis

AU - Tósaki, A.

AU - Das, Dipak K.

PY - 2001/9/15

Y1 - 2001/9/15

N2 - The mechanism of cardioprotection with red wine consumption was studied by examining the antideath signaling cascade of one of the principle components of red wine, proanthocyanidins. Grape seed proanthocyanidin extract (GSPE) was administered orally (100 mg/kg/d) supplemented with regular diet for 3 weeks to a group of rats while the other group was given the regular diet only for the same period of time. After 3 weeks, rats were sacrificed, hearts excised, and perfused via Langendorff mode. After stabilization, hearts were perfused in the working mode for baseline measurement of contractile function. Hearts were then made globally ischemic for 30 min followed by 2 h of reperfusion. Contratile function was continuously monitored during reperfusion, and free radical production was examined by electron spin resonance (ESR) technique. Cardiomyocyte apoptosis was examined by TUNEL staining in conjunction with an antibody against myocin heavy chain to specifically detect myocytes. Induction of JNK-1 and c-fos proteins was studied by Western blot analysis using respective antibodies followed by densitometric scanning. The results indicated significant induction of JNK-1 and c-fos proteins in the ischemic/reperfused myocardium, which was inhibited by the proanthocyanidin extract. In concert, GSPE significantly reduced the appearance of apoptotic cardiomyocytes in the ischemic/reperfused hearts. GSPE also significantly reduced the appearance of the reactive oxygen species in the hearts. Improved postischemic contractile recovery was achieved with GSPE suggesting its cardioprotective action. The results of this study indicated that GSPE functioned as an in vivo antioxidant, and its cardioprotective properties may be at least partially attributed to its ability to block antideath signal through the inhibition of proapoptotic transcription factor and gene, JNK-1 and c-Jun.

AB - The mechanism of cardioprotection with red wine consumption was studied by examining the antideath signaling cascade of one of the principle components of red wine, proanthocyanidins. Grape seed proanthocyanidin extract (GSPE) was administered orally (100 mg/kg/d) supplemented with regular diet for 3 weeks to a group of rats while the other group was given the regular diet only for the same period of time. After 3 weeks, rats were sacrificed, hearts excised, and perfused via Langendorff mode. After stabilization, hearts were perfused in the working mode for baseline measurement of contractile function. Hearts were then made globally ischemic for 30 min followed by 2 h of reperfusion. Contratile function was continuously monitored during reperfusion, and free radical production was examined by electron spin resonance (ESR) technique. Cardiomyocyte apoptosis was examined by TUNEL staining in conjunction with an antibody against myocin heavy chain to specifically detect myocytes. Induction of JNK-1 and c-fos proteins was studied by Western blot analysis using respective antibodies followed by densitometric scanning. The results indicated significant induction of JNK-1 and c-fos proteins in the ischemic/reperfused myocardium, which was inhibited by the proanthocyanidin extract. In concert, GSPE significantly reduced the appearance of apoptotic cardiomyocytes in the ischemic/reperfused hearts. GSPE also significantly reduced the appearance of the reactive oxygen species in the hearts. Improved postischemic contractile recovery was achieved with GSPE suggesting its cardioprotective action. The results of this study indicated that GSPE functioned as an in vivo antioxidant, and its cardioprotective properties may be at least partially attributed to its ability to block antideath signal through the inhibition of proapoptotic transcription factor and gene, JNK-1 and c-Jun.

KW - Alcohol

KW - Apoptosis

KW - C-Jun

KW - Cardiomyocytes

KW - Free radicals

KW - Heart

KW - JNK

KW - Proanthocyanidins

KW - Wine

UR - http://www.scopus.com/inward/record.url?scp=0035884851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035884851&partnerID=8YFLogxK

U2 - 10.1016/S0891-5849(01)00626-8

DO - 10.1016/S0891-5849(01)00626-8

M3 - Article

C2 - 11557310

AN - SCOPUS:0035884851

VL - 31

SP - 729

EP - 737

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 6

ER -