Fluidising effect of resorcylidene aminoguanidine on sarcolemmal membranes in streptozotocin-diabetic rats: blunted adaptation of diabetic myocardium to Ca2+ overload.
The "remodelling" of cardiac sarcolemma in diabetes is believed to underlie the reduced sensitivity of diabetic hearts due to their overload with extracellular calcium. Along with a non-enzymatic glycosylation and the free radical-derived glycoxidation of sarcolemmal proteins there is ongoing reduction in cardiomyocyte membrane fluidity, the modulator of cardiac sarcolemmal functioning. Aminoguanidine derivatives, that inhibit glycation and glycoxidation, might suppress myocardium "remodelling" occurring in diabetic heart. To verify this hypothesis, we studied physical parameters of cardiac sarcolemma from the streptozotocin-induced diabetic rats (45 mg.kg(-1) i.m.) treated with resorcylidene aminoguanidine (RAG, 4 or 8 mg.kg(-1) i.m.). The treatment with RAG not only completely abolished protein glycation and a generation of free oxygen species (p < 0.001) in treated diabetic animals, but also considerably attenuated the decrease in sarcolemmal membrane fluidity (p < 0.001). In diabetic animals the "normalization" of the sarcolemmal membrane fluidity was accompanied by the vastly increased susceptibility of diabetic hearts to be overload with external calcium. We concluded that the decreased fluidity of the sarcolemmal membrane, apparently linked to the excessive glycation of sarcolemmal membrane proteins, might be intimately connected with the adaptation mechanism(s) that are likely to develop in diabetic heart to protect it against the overload with external calcium.
Waczulíková
I
I
Department of Biophysics and Chemical Physics, Faculty of Mathematics, Physics, and Informatics, Comenius University, Bratislava, Slovakia. waczulikova@fmph.uniba.sk
Ziegelhöffer
A
A
Országhová
Z
Z
Cársky
J
J
D000222:Adaptation, Physiological; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D019270:Fructosamine / Q000097:blood; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*
D001786:Blood Glucose; D006146:Guanidines; C115168:resorcylidene aminoguanidine; D019270:Fructosamine; D002118:Calcium