Combined calcium carbimide and ethanol treatment induces high blood acetaldehyde levels, myocardial apoptosis and altered expression of apoptosis-regulating genes in rat.
The effects of ethanol and ethanol-derived acetaldehyde on rat myocardial apoptosis and expression of genes involved in the regulation of apoptosis and cell cycle arrest were studied. Combined ethanol and calcium carbimide treatment for 2, 5 or 8 days (E + CC) markedly increased blood acetaldehyde levels. Cytosolic DNA fragmentation was quantified in the 5-day treatment group. Increased amount of DNA-fragmentation, reflecting increased apoptosis, was evident in the E + CC group (23% increase compared to controls). mRNA levels of genes regulating apoptosis were measured by using quantitative PCR in the 2- and 8-day treatment groups. In the 2-day treatment group, p21 gene expression was increased by 25% and bax/bcl-2 mRNA ratio by 57% in E + CC, compared to the control, group. In the 8-day treatment group, p21 mRNA level was 24% lower, p53 mRNA level was 15% higher (P < 0.005), and bcl-2 mRNA level 36% higher in E + CC-treated, compared to the control, group. Interestingly, both ethanol and calcium carbimide treatments alone increased bax mRNA levels, as compared to the control group at 2 and 8 days. These results indicate that acetaldehyde might regulate the expression of apoptosis-linked genes and that apoptosis of myocardial cells may be involved in the development of alcoholic heart disease.
Jänkälä
Heidi
H
Department of Clinical Chemistry, Helsinki University Central Hospital, Haartmaninkatu 4, SF-00290, Finland.
Eriksson
C J Peter
CJ
Eklund
Kari K
KK
Härkönen
Matti
M
Mäki
Tiina
T
D000079:Acetaldehyde / Q000097:blood*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003484:Cyanamide / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D004338:Drug Combinations; D000431:Ethanol; D003484:Cyanamide; D000079:Acetaldehyde