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

  • Barbara Ziegelhöffer-Mihalovičová
  • Iveta Waczulíková
  • Libuša Šikurová
  • Ján Styk
  • Jozef Čársky
  • Attila Ziegelhöffer
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 42)

Abstract

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 μg.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 μmol.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. (Mol Cell Biochem 249: 175–182, 2003)

Key words

diabetic heart membrane fluidity protein glycation calcium tolerance glycoxidation resorcylidene aminoguanidine 

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Copyright information

© Springer Science+Business Media New York  2003

Authors and Affiliations

  • Barbara Ziegelhöffer-Mihalovičová
    • 1
  • Iveta Waczulíková
    • 2
  • Libuša Šikurová
    • 2
  • Ján Styk
    • 1
  • Jozef Čársky
    • 3
  • Attila Ziegelhöffer
    • 1
  1. 1.Institute for Heart ResearchSlovak Academy of SciencesBratislava
  2. 2.Department of Biophysics and Chemical Physics, Faculty of MathematicsPhysics, and Informatics, Comenius UniversityMlynská dolinaBratislava
  3. 3.Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of MedicineComenius University, SasinkovaBratislavaSlovak Republic

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