المؤلفون: Morris Karmazyn, Lorrie A. Kirshenbaum, Cathy Huang, Sabzali Javadov

المصدر: Journal of Molecular and Cellular Cardiology. 38:135-143

مصطلحات موضوعية: Male, medicine.medical_specialty, Sodium-Hydrogen Exchangers, Cell Respiration, chemistry.chemical_element, Citrate (si)-Synthase, Calcium, Guanidines, Mitochondria, Heart, Permeability, Muscle hypertrophy, Rats, Sprague-Dawley, chemistry.chemical_compound, Internal medicine, medicine, Animals, Respiratory function, Sulfones, Molecular Biology, Isolated mitochondria, Chemistry, Myocardium, Body Weight, Intracellular Membranes, Organ Size, medicine.disease, Rats, Surgery, Adenosine Diphosphate, Disease Models, Animal, EGTA, Endocrinology, Mitochondrial permeability transition pore, Infarction, Heart failure, Cardiology and Cardiovascular Medicine, Ligation

الوصف: The mechanism by which Na+-H+ exchange (NHE) inhibition results in attenuation and reversal of postinfarction remodelling and heart failure remains controversial. In this study, we investigated the possible contribution of mitochondrial involvement by determining the effect of the NHE-1-specific inhibitor EMD-87580 (EMD) on mitochondrial permeability transition (MPT) and respiratory function during the postinfarction remodelling process. Male Sprague-Dawley rats were subjected to either 12 or 18 weeks of coronary artery ligation (CAL) or sham procedure. EMD was provided in the diet immediately after ligation. MPT pore opening was determined by perfusing hearts with 2-deoxy-[3H]-glucose ([3H]-DOG) and measurement of mitochondrial [3H]-DOG entrapment. The respiratory function of isolated mitochondria was measured using Clark-type oxygen electrode. Remodelling was associated with significant hypertrophy and there was an increase in MPT pore opening in hearts both 12 and 18 weeks following CAL. Mitochondrial respiratory function, especially state 2 and state 3 rates were significantly decreased in hearts subjected to CAL. EMD suppressed MPT pore opening by 40% (P0.01) and 35% (P0.01) 12 and 18 weeks after ligation, respectively. Mitochondria isolated from EMD treated hearts exhibited increased respiratory chain activity for oxidation of substrates at complex I and II. These beneficial effects of EMD were associated with decreased mitochondrial vulnerability to exogenous Ca2+. We conclude that NHE-1 inhibition has a protective effect on mitochondrial function, attenuating MPT pore opening and improving the respiratory function, which may contribute to the salutary effect of NHE-1 inhibitors in heart failure.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::86453d062d8f17878dcded420ebd6ebfTest
https://doi.org/10.1016/j.yjmcc.2004.10.007Test

المؤلفون: Lorrie A. Kirshenbaum, Igor Danelisen, Timao Li, Dinender Kumar, Pawan K. Singal

المصدر: Antioxidantsredox signaling. 3(1)

مصطلحات موضوعية: Male, medicine.medical_specialty, Time Factors, Physiology, Clinical Biochemistry, Cardiomyopathy, Probucol, Caspase 3, Antineoplastic Agents, Apoptosis, medicine.disease_cause, Biochemistry, Rats, Sprague-Dawley, Bcl-2-associated X protein, Internal medicine, Proto-Oncogene Proteins, medicine, Animals, Doxorubicin, Molecular Biology, Caspase, General Environmental Science, bcl-2-Associated X Protein, Cell Nucleus, Heart Failure, biology, business.industry, Myocardium, Hemodynamics, Heart, Cell Biology, medicine.disease, Rats, Endocrinology, Proto-Oncogene Proteins c-bcl-2, Caspases, Immunology, biology.protein, General Earth and Planetary Sciences, business, Cardiomyopathies, Oxidative stress, medicine.drug

الوصف: The dose-dependent cardiomyopathy and heart failure due to adriamycin have been shown to be due to increased oxidative stress and loss of myocytes. We examined the incidence of myocardial apoptosis as well as changes in the expression of apoptotic regulatory gene products in an established animal model of adriamycin cardiomyopathy. Rats were treated with adriamycin (cumulative dose, 15 mg/kg), and the hearts were examined for apoptosis as well as expression of Bax, caspase 3, and Bcl-2 at 0, 4, 10, 16, and 21 days after the treatment. A significant increase in the incidence of apoptosis was seen at 4 days, followed by a decline at 10 and 16 days of posttreatment. At 21 days, the number of apoptotic cells increased again and included cells of the conducting system. Expression of Bax corresponded to these biphasic changes, whereas the converse was true for the expression of Bcl-2. The latter peaked at 10 days followed by a decline at 16 and 21 days. The Bax/Bcl-2 ratio also correlated with the incidence of apoptosis. Expression of caspase 3 correlated with increased apoptosis, but only at early time points. Probucol (cumulative dose, 120 mg/kg), a known antioxidant as well as promoter of endogenous antioxidants, significantly reduced the incidence of apoptosis as well as expression of Bax. Adriamycin-induced hemodynamic changes were also prevented by probucol. These data suggest that adriamycin-induced apoptosis is mediated by oxidative stress and may play a role in the development of heart failure.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0b5d72cc661e943687c015af40b689fTest
https://pubmed.ncbi.nlm.nih.gov/11291592Test