Modulation of adenine nucleotide translocase activity during myocardial ischemia

A. L. Shug, Ramiah Subramanian

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Preliminary studies have shown that high levels of free fatty acids, which elevate LCACAE and lower levels of free carnitine, are much more harmful to the heart after repeated periods of ischemia and reperfusion than after exposure to continuous ischemia and reperfusion. These observations appear to support our hypothesis that LCACAE inhibition of the mitochondrial ANT during ischemia potentiates free radical mediated damage to the inner mitochondrial membrane during reperfusion. These and related findings by others have led us to hypothesize that the mechanisms of ischemic injury to the heart involve the following sequence of events: (1) exposure to high levels of FFA during ischemia and reperfusion results in permanently elevated LCACAE and low free carnitine levels; (2) LCACAE-ANT binding increases and ANT activity decreases; (3) mitochondrial swelling occurs because of decreased ADP/ATP transport and oxidative phosphorylation; (4) complex III activity is altered (superoxide formation increases), and swelling of mitochondrial membranes exposes C = C bonds that are required for lipid peroxidation, which can lead to inner mitochondrial membrane damage. We further hypothesize that LCACAE-ANT inhibition-induced free radical damage causes the loss of mitochondrial matrix components (22), eventually leading to lesions of the sarcolemmal membrane and cell necrosis (22). Studies now in progress support this hypothesis and indicate that inhibition of ANT in isolated rat heart mitochondria by carboxyatractyloside or palmitoyl CoA stimulates free radical formation, probably at the complex III loci. Stimulation of free radical formation by palmitoyl CoA was reversed by L-carnitine. These findings, if substantiated by further studies, may provide the first evidence that L-carnitine protects the ischemic heart from free radical damage.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
JournalZeitschrift fur Kardiologie
Volume76
Issue numberSUPPL. 5
StatePublished - Dec 1 1987

Fingerprint

ATP Translocases Mitochondrial ADP
Carnitine
Free Radicals
Myocardial Ischemia
Reperfusion
Mitochondrial Membranes
Ischemia
Palmitoyl Coenzyme A
Electron Transport Complex III
Heart Injuries
Mitochondrial Swelling
Heart Mitochondria
Oxidative Phosphorylation
Nonesterified Fatty Acids
Superoxides
Adenosine Diphosphate
Lipid Peroxidation
Necrosis
Adenosine Triphosphate
Cell Membrane

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Modulation of adenine nucleotide translocase activity during myocardial ischemia. / Shug, A. L.; Subramanian, Ramiah.

In: Zeitschrift fur Kardiologie, Vol. 76, No. SUPPL. 5, 01.12.1987, p. 26-33.

Research output: Contribution to journalArticle

Shug, A. L. ; Subramanian, Ramiah. / Modulation of adenine nucleotide translocase activity during myocardial ischemia. In: Zeitschrift fur Kardiologie. 1987 ; Vol. 76, No. SUPPL. 5. pp. 26-33.
@article{3cb7e68c4be24028a050058c809dad62,
title = "Modulation of adenine nucleotide translocase activity during myocardial ischemia",
abstract = "Preliminary studies have shown that high levels of free fatty acids, which elevate LCACAE and lower levels of free carnitine, are much more harmful to the heart after repeated periods of ischemia and reperfusion than after exposure to continuous ischemia and reperfusion. These observations appear to support our hypothesis that LCACAE inhibition of the mitochondrial ANT during ischemia potentiates free radical mediated damage to the inner mitochondrial membrane during reperfusion. These and related findings by others have led us to hypothesize that the mechanisms of ischemic injury to the heart involve the following sequence of events: (1) exposure to high levels of FFA during ischemia and reperfusion results in permanently elevated LCACAE and low free carnitine levels; (2) LCACAE-ANT binding increases and ANT activity decreases; (3) mitochondrial swelling occurs because of decreased ADP/ATP transport and oxidative phosphorylation; (4) complex III activity is altered (superoxide formation increases), and swelling of mitochondrial membranes exposes C = C bonds that are required for lipid peroxidation, which can lead to inner mitochondrial membrane damage. We further hypothesize that LCACAE-ANT inhibition-induced free radical damage causes the loss of mitochondrial matrix components (22), eventually leading to lesions of the sarcolemmal membrane and cell necrosis (22). Studies now in progress support this hypothesis and indicate that inhibition of ANT in isolated rat heart mitochondria by carboxyatractyloside or palmitoyl CoA stimulates free radical formation, probably at the complex III loci. Stimulation of free radical formation by palmitoyl CoA was reversed by L-carnitine. These findings, if substantiated by further studies, may provide the first evidence that L-carnitine protects the ischemic heart from free radical damage.",
author = "Shug, {A. L.} and Ramiah Subramanian",
year = "1987",
month = "12",
day = "1",
language = "English (US)",
volume = "76",
pages = "26--33",
journal = "Clinical Research in Cardiology",
issn = "1861-0684",
publisher = "D. Steinkopff-Verlag",
number = "SUPPL. 5",

}

TY - JOUR

T1 - Modulation of adenine nucleotide translocase activity during myocardial ischemia

AU - Shug, A. L.

AU - Subramanian, Ramiah

PY - 1987/12/1

Y1 - 1987/12/1

N2 - Preliminary studies have shown that high levels of free fatty acids, which elevate LCACAE and lower levels of free carnitine, are much more harmful to the heart after repeated periods of ischemia and reperfusion than after exposure to continuous ischemia and reperfusion. These observations appear to support our hypothesis that LCACAE inhibition of the mitochondrial ANT during ischemia potentiates free radical mediated damage to the inner mitochondrial membrane during reperfusion. These and related findings by others have led us to hypothesize that the mechanisms of ischemic injury to the heart involve the following sequence of events: (1) exposure to high levels of FFA during ischemia and reperfusion results in permanently elevated LCACAE and low free carnitine levels; (2) LCACAE-ANT binding increases and ANT activity decreases; (3) mitochondrial swelling occurs because of decreased ADP/ATP transport and oxidative phosphorylation; (4) complex III activity is altered (superoxide formation increases), and swelling of mitochondrial membranes exposes C = C bonds that are required for lipid peroxidation, which can lead to inner mitochondrial membrane damage. We further hypothesize that LCACAE-ANT inhibition-induced free radical damage causes the loss of mitochondrial matrix components (22), eventually leading to lesions of the sarcolemmal membrane and cell necrosis (22). Studies now in progress support this hypothesis and indicate that inhibition of ANT in isolated rat heart mitochondria by carboxyatractyloside or palmitoyl CoA stimulates free radical formation, probably at the complex III loci. Stimulation of free radical formation by palmitoyl CoA was reversed by L-carnitine. These findings, if substantiated by further studies, may provide the first evidence that L-carnitine protects the ischemic heart from free radical damage.

AB - Preliminary studies have shown that high levels of free fatty acids, which elevate LCACAE and lower levels of free carnitine, are much more harmful to the heart after repeated periods of ischemia and reperfusion than after exposure to continuous ischemia and reperfusion. These observations appear to support our hypothesis that LCACAE inhibition of the mitochondrial ANT during ischemia potentiates free radical mediated damage to the inner mitochondrial membrane during reperfusion. These and related findings by others have led us to hypothesize that the mechanisms of ischemic injury to the heart involve the following sequence of events: (1) exposure to high levels of FFA during ischemia and reperfusion results in permanently elevated LCACAE and low free carnitine levels; (2) LCACAE-ANT binding increases and ANT activity decreases; (3) mitochondrial swelling occurs because of decreased ADP/ATP transport and oxidative phosphorylation; (4) complex III activity is altered (superoxide formation increases), and swelling of mitochondrial membranes exposes C = C bonds that are required for lipid peroxidation, which can lead to inner mitochondrial membrane damage. We further hypothesize that LCACAE-ANT inhibition-induced free radical damage causes the loss of mitochondrial matrix components (22), eventually leading to lesions of the sarcolemmal membrane and cell necrosis (22). Studies now in progress support this hypothesis and indicate that inhibition of ANT in isolated rat heart mitochondria by carboxyatractyloside or palmitoyl CoA stimulates free radical formation, probably at the complex III loci. Stimulation of free radical formation by palmitoyl CoA was reversed by L-carnitine. These findings, if substantiated by further studies, may provide the first evidence that L-carnitine protects the ischemic heart from free radical damage.

UR - http://www.scopus.com/inward/record.url?scp=0023491222&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023491222&partnerID=8YFLogxK

M3 - Article

C2 - 2829452

AN - SCOPUS:0023491222

VL - 76

SP - 26

EP - 33

JO - Clinical Research in Cardiology

JF - Clinical Research in Cardiology

SN - 1861-0684

IS - SUPPL. 5

ER -