Molecular changes in erythrocyte membranes induced by long-term administration of clofibrate.
It has been reported that an enantiomer ((S)-(-)-4) of clofibric acid, and the racemate, can block the chloride conductance of skeletal muscle membrane. It has also been reported that several analogs of clofibric acid inhibit the HCO3(-)-Cl- exchange of erythrocytes. Since the two effects are probably similar biophysical membrane phenomena, the possibility of a common molecular mechanism arises. We exposed Sprague-Dawley male rats to long-term administration of clofibrate and 20,25-diazacholesterol (20,25-D) for comparison, at equipotent doses. Clofibrate (but not 20,25-diazacholesterol) produced a significant increase in density of the 220,000 Da band (beta-spectrin) and a decrease, also significant, in density of bands 2.1, 2.2, 2.3, 2.6 (syndeins or ankyrins) and of bands 4.1 and 6. Thus, clofibrate exhibits a manifold effect on the protein profile of the erythrocyte membrane cytoskeleton which, due to the lack of effect of 20-25-D, does not seem to be produced by the hypolipidemic effect per se, and thus deserves further study.
División de Farmacología, Unidad de Investigación Biomédica del Noreste, Monterrey, N.L., Mexico.
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Morales-Aguilera
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Sampayo-Reyes
D000818:Animals; D001373:Azacosterol / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D003720:Densitometry; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007202:Indicators and Reagents; D008297:Male; D008855:Microscopy, Electron, Scanning; D009996:Osmotic Fragility / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001798:Blood Proteins; D007202:Indicators and Reagents; D002784:Cholesterol; D001373:Azacosterol; D002994:Clofibrate