Back to Search
Start Over
Attenuation of fatty acid-induced apoptosis by low-dose alcohol in neonatal rat cardiomyocytes
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 287:H2209-H2215
- Publication Year :
- 2004
- Publisher :
- American Physiological Society, 2004.
-
Abstract
- Moderate alcohol consumption has been shown to reduce the morbidity and mortality from coronary heart disease. Ethanol elicits its protective effects via mechanisms that include activation of protein kinases linked to growth and survival. Our results in isolated neonatal rat cardiomyocytes demonstrate that repeated short-term, low-dose exposure to ethanol is sufficient to activate the growth and/or survival pathways that involve PKC-ε, Akt, and AMP-activated kinase. In addition, we are able to induce apoptosis in these cardiomyocytes using the saturated fatty acid palmitate. Pretreatment with multiple low-dose ethanol exposures attenuates the apoptotic response to palmitate. This protection is manifested by a reduction in caspase-3-like activity, decreased mitochondrial loss of cytochrome c, and decreased loss of the mitochondrial lipid cardiolipin. We previously reported that incubation of cardiomyocytes with palmitate results in decreased production of reactive oxygen species compared with cells incubated with the nonapoptotic fatty acid oleate. In the present study, we observed an increase in the production of superoxide and the rates of fatty acid oxidation in cardiomyocytes pretreated with ethanol and then exposed to fatty acids. The level of superoxide production in palmitate-treated cells returns to the levels observed in oleate-treated cells after ethanol exposure. Taken together with our observed increase in AMP-activated kinase activity, we propose that ethanol pretreatments stimulate oxidative metabolism and electron transport within cardiomyocytes. We postulate that stimulation of palmitate metabolism may protect cardiomyocytes by preventing accumulation of unsaturated precursor molecules of cardiolipin synthesis. Maintaining cardiolipin levels may be sufficient to prevent the mitochondrial loss of cytochrome c and the downstream activation of caspases.
- Subjects :
- medicine.medical_specialty
Time Factors
Physiology
Palmitic Acid
Apoptosis
Alcohol
Protein Kinase C-epsilon
AMP-Activated Protein Kinases
Protein Serine-Threonine Kinases
Biology
Rats, Sprague-Dawley
chemistry.chemical_compound
Multienzyme Complexes
Superoxides
Proto-Oncogene Proteins
Physiology (medical)
Internal medicine
Cardiolipin
medicine
Animals
Myocytes, Cardiac
Cells, Cultured
Protein Kinase C
chemistry.chemical_classification
Reactive oxygen species
Ethanol
Dose-Response Relationship, Drug
Models, Cardiovascular
Fatty acid
Rats
Enzyme
Endocrinology
Animals, Newborn
chemistry
Toxicity
Cardiology and Cardiovascular Medicine
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 287
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....276f2da3ecb24a1c9b33fc1838e0facf
- Full Text :
- https://doi.org/10.1152/ajpheart.00247.2004