Antioxidant therapy attenuates JNK activation and apoptosis in the remote noninfarcted myocardium after large myocardial infarction.
We hypothesized that the concomitant occurrence of increased oxidative stress, JNK activation, and myocyte apoptosis in the remote myocardium (RM) following a large myocardial infarction (MI) are causally related. Three days following coronary ligation, rats were randomized to treatment with probucol and PDTC (MI-T) or vehicle (MI). Control rats (C) underwent sham operation. At 7 weeks, TBARS assay showed increased level of lipid-peroxidation within the RM in the MI group vs C, which was completely inhibited in the MI-T group. Similarly, Western blot analysis showed a twofold increase in p-JNK in the MI group, vs C, which was attenuated in MI-T, a result confirmed by a JNK-kinase activity. Furthermore, apoptosis was increased within the RM in MI vs C, while this was inhibited in MI-T. We conclude that long-term antioxidant therapy with probucol and PDTC attenuates oxidative stress, JNK activation, and myocyte apoptosis within the RM after large MI.
Li
W G
WG
Department of Internal Medicine, University of Iowa, Iowa City, USA.
Coppey
L
L
Weiss
R M
RM
Oskarsson
H J
HJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011341:Probucol / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D000975:Antioxidants; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D011392:Proline; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011341:Probucol