Remodelling of the sarcolemma in diabetic rat hearts: the role of membrane fluidity

• Published in: Molecular and cellular biochemistry 2003-07, Vol.249 (1-2), p.175-182
• Main Authors: Ziegelhöffer-Mihalovicová, Barbara, Waczulíková, Iveta, Sikurová, Libusa, Styk, Ján, Cársky, Jozef, Ziegelhöffer, Attila
• Format: Article
• Language: English
• Subjects: Animals; Anisotropy; Calcium-Transporting ATPases - metabolism; Cells, Cultured; Diabetes; Diabetes Mellitus, Experimental - metabolism; Guanidines - pharmacology; Heart - physiopathology; Membrane Fluidity - physiology; Membranes; Myocardium - pathology; Oxidative stress; Rats; Rats, Wistar; Rodents; Sarcolemma - drug effects; Sarcolemma - metabolism; Sarcolemma - pathology; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/A:1024703226034

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.