Ethanol-induced inhibition of ventricular protein synthesis in vivo and the possible role of acetaldehyde.
We have determined the extent to which acute ethanol administration perturbs the synthesis of ventricular contractile and non-contractile proteins in vivo. Male Wistar rats were treated with a standard dose of ethanol (75 mmol kg-1 body weight; i.p.). Controls were treated with isovolumetric amounts of saline (0.15 mol l-1 NaCl). Two metabolic inhibitors of ethanol metabolism were also used namely 4-methylpyrazole (alcohol dehydrogenase inhibitor) and cyanamide (acetaldehyde dehydrogenase inhibitor) which in ethanol-dosed rats have been shown to either decrease or increase acetaldehyde formation, respectively. After 2.5 h, fractional rates of protein synthesis (i.e. the percentage of tissue protein renewed each day) were measured with a large (i.e. 'flooding') dose of L-[4-3H]phenylalanine (150 mumol (100 g)-1 body weight into a lateral vein). This dose of phenylalanine effectively floods all endogenous free amino acid pools so that the specific radioactivity of the free amino acid at the site of protein synthesis (i.e. the amino acyl tRNA) is reflected by the specific radioactivity of the free amino acid in acid-soluble portions of cardiac homogenates. The results showed that ethanol alone and ethanol plus 4-methylpyrazole decreased the fractional rates of mixed, myofibrillar (contractile) and sarcoplasmic (non-contractile) protein synthesis to the same extent (by approx. 25 per cent). Profound inhibition (i.e. 80 per cent) in the fractional rates of mixed, myofibrillar and sarcoplasmic protein synthesis occurred when cyanamide was used to increase acetaldehyde formation. There was also a significant decrease in cardiac DNA content. The results suggest that acute ethanol-induced cardiac injury in the rat may be mediated by both acetaldehyde and ethanol.
Siddiq
T
T
Department of Cardiology, King's College School of Medicine and Dentistry, London, U.K.
Richardson
P J
PJ
Mitchell
W D
WD
Teare
J
J
Preedy
V R
VR
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D002310:Cardiomyopathy, Alcoholic / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology; D003864:Depression, Chemical; D000431:Ethanol / Q000494:pharmacology*; D000077604:Fomepizole; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D009124:Muscle Proteins; D011500:Protein Synthesis Inhibitors; D011720:Pyrazoles; D000431:Ethanol; D003484:Cyanamide; D000077604:Fomepizole; D000079:Acetaldehyde