Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-10
pubmed:abstractText
Skeletal muscle atrophy is a common feature in alcoholism that affects up to two-thirds of alcohol misusers, and women appear to be particularly susceptible. There is also some evidence to suggest that malnutrition exacerbates the effects of alcohol on muscle. However, the mechanisms responsible for the myopathy remain elusive, and some studies suggest that acetaldehyde, rather than alcohol, is the principal pathogenic perturbant. Previous reports on rats dosed acutely with ethanol (<24 h) have suggested that increased proto-oncogene expression (i.e., c-myc) may be a causative process, possibly via activating preapoptotic or transcriptional pathways. We hypothesized that 1) increases in c-myc mRNA levels also occur in muscle exposed chronically to alcohol, 2) muscle of female rats is more sensitive than that from male rats, 3) raising acetaldehyde will also increase c-myc, 4) prior starvation will cause further increases in c-myc mRNA expression in response to ethanol, and 5) other genes involved in apoptosis (i.e., p53 and Bcl-2) would also be affected by alcohol. To test this, we measured c-myc mRNA levels in skeletal muscle of rats dosed either chronically (6-7 wk; ethanol as 35% of total dietary energy) or acutely (2.5 h; ethanol as 75 mmol/kg body wt ip) with ethanol. All experiments were carried out in male Wistar rats (approximately 0.1-0.15 kg body wt) except the study that examined gender susceptibility in male and female rats. At the end of the studies, rats were killed, and c-myc, p53, and Bcl-2 mRNA was analyzed in skeletal muscle by RT-PCR with an endogenous internal standard, GAPDH. The results showed that 1) in male rats fed ethanol chronically, there were no increases in c-myc mRNA; 2) increases, however, occurred in c-myc mRNA in muscle from female rats fed ethanol chronically; 3) raising endogenous acetaldehyde with cyanamide increased c-myc mRNA in acute studies; 4) starvation per se increased c-myc mRNA levels and at 1 day potentiated the acute effects of ethanol, indicative of a sensitization response; 5) the only effect seen with p53 mRNA levels was a decrease in muscle of rats starved for 1 day compared with fed rats, and there was no statistically significant effect on Bcl-2 mRNA in any of the experimental conditions. The increases in c-myc may well represent a preapoptotic effect, or even a nonspecific cellular stress response to alcohol and/or acetaldehyde. These data are important in our understanding of a common muscle pathology induced by alcohol.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E1273-81
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12876071-Alcoholic Intoxication, pubmed-meshheading:12876071-Animals, pubmed-meshheading:12876071-Cyanamide, pubmed-meshheading:12876071-Ethanol, pubmed-meshheading:12876071-Female, pubmed-meshheading:12876071-Male, pubmed-meshheading:12876071-Muscle, Skeletal, pubmed-meshheading:12876071-Muscle Weakness, pubmed-meshheading:12876071-Proto-Oncogene Proteins, pubmed-meshheading:12876071-Proto-Oncogene Proteins c-myc, pubmed-meshheading:12876071-RNA, Messenger, pubmed-meshheading:12876071-Rats, pubmed-meshheading:12876071-Rats, Wistar, pubmed-meshheading:12876071-Sex Factors, pubmed-meshheading:12876071-Starvation, pubmed-meshheading:12876071-Toxicity Tests, Acute, pubmed-meshheading:12876071-Toxicity Tests, Chronic, pubmed-meshheading:12876071-Tumor Suppressor Protein p53
pubmed:year
2003
pubmed:articleTitle
Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression.
pubmed:affiliation
Department of Chemistry, Faculty of Science, Kyushu University Ropponmatsu, Fukuoka 810-8560, Japan.
pubmed:publicationType
Journal Article, Comparative Study