No correlation between the p38 MAPK pathway and the contractile dysfunction in diabetic cardiomyocytes: hyperglycaemia-induced signalling and contractile function.
Besides the classical cardiovascular diseases, high levels of blood glucose directly interfere with cardiomyocytes. The mechanisms responsible for this have not yet been explored in detail. This study aims to determine if hyperglycaemia has any impact on prominent signalling molecules and on the contractile function of cardiomyocytes. Freshly isolated cardiomyocytes from adult rats were treated with various concentrations of glucose. Formed free radicals were measured by DCF-fluorescence. TGFbeta expression and p38 MAP-kinase (MAPK) activation were measured by Western blotting. The contractile efficiency was determined by measurement of the maximal amount of cell shortening. Glucose (30 mM) caused an increase in formation of radicals, phosphorylation of p38 MAPK, and TGFbeta expression. Under conditions of low viscosity (1 cp), contractile responses to hyperglycaemia (15 mM) were not altered in contrast to control. However, enhancement of viscosity (400 cp) effected a limitation of contractile function. The responsiveness to beta-adrenoceptor stimulation did not change. Neither inhibition of p38 MAPK with SB 202190 (1 microM) nor inhibition of reactive oxygen species with vitamin C did alter these measured functional parameters. Diabetes mellitus directly influences the activation degree of prominent signalling molecules and the contractile function of adult ventricular cardiomyocytes, which results in facilitating in the development of diabetic cardiomyopathy.
Wenzel
Sibylle
S
Physiologisches Institut, Justus-Liebig-Universität, Aulweg 129, 35392 Giessen, Germany. sibylle.wenzel@physiologie.med.uni-giessen.de
Soltanpour
Golozar
G
Schlüter
Klaus-Dieter
KD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000975:Antioxidants; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D007545:Isoproterenol; D001205:Ascorbic Acid; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole