Remodelling of the sarcolemma in diabetic rat hearts: the role of membrane fluidity.
The hyperglycaemia and oxidative stress, that occur in diabetes mellitus, cause impairment of membrane functions in cardiomyocytes. Also reduced sensitivity to Ca-overload was reported in diabetic hearts (D). This enhanced calcium resistance is based on remodelling of the sarcolemmal membranes (SL) with down-regulated, but from the point of view of kinetics relatively well preserved Na,K-ATPase and abnormal Mg- and Ca-ATPase (Mg/Ca-ATPase) activities. It was hypothesised that in these changes may also participate the non-enzymatic glycation of proteins (NEG) and the related free radical formation (FRF), that decrease the membrane fluidity (SLMF), which is in reversal relationship to the fluorescence anisotropy (D 0.235 +/- 0.022; controls (C) 0.185 +/- 0.009; p < 0.001). In order to check the true role of SLMF in hearts of the diabetic rats (streptozotocin, single dose, 45 mg/kg i.v.) animals were treated in a special regimen with resorcylidene aminoguanidine (RAG 4 mg/kg i.m.). The treatment with RAG eliminated completely the diabetes-induced decrease in the SLMF (C 0.185 +/- 0.009; D + RAG 0.167 +/- 0.013; p < 0.001) as well as in NEG (fructosamine microg x mg(-1) of protein: C 2.68 +/- 0.14; D 4.48 +/- 0.85; D + RAG 2.57 +/- 0.14; p < 0.001), and FRF in the SL (malondialdehyde: C 5.3 +/- 0.3; D 8.63 +/- 0.2; D + RAG 5.61 +/- 0.53 micromol x g(-1); p < 0.05). Nevertheless, the SL ATPase activity in diabetic animals was not considerably influenced by RAG (increase in D + RAG vs. D 3.3%, p > 0.05). On the other hand, RAG increased considerably the vulnerability of the diabetic heart to overload with external Ca2+ (C 100% of hearts failed, D 83.3%, D + RAG 46.7% of hearts survived). So we may conclude, that: (i) The NEG and FRF caused alterations in SLMF, that accompanied the diabetes-induced remodelling of SL, also seem to participate in the protection of diabetic heart against Ca2+-overload; (ii) Although, the changes in SLMF were shown to influence considerably the ATPase activities in cells of diverse tissues, they seem to be little responsible for changes in ATPases-mediated processes in the SL of chronic diabetic hearts.
Ziegelhöffer-Mihalovicová
Barbara
B
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic. zieb@medizin.uni-leipzig.de
Waczulíková
Iveta
I
Sikurová
Libusa
L
Styk
Ján
J
Cársky
Jozef
J
Ziegelhöffer
Attila
A
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000503:physiopathology*; D008560:Membrane Fluidity / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D006146:Guanidines; C115168:resorcylidene aminoguanidine; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase