No correlation between the p38 MAPK pathway and the contractile dysfunction in diabetic cardiomyocytes

Abstract

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.

Altered Expression and Activation of Mitogen-Activated Protein Kinases in Diabetic Heart During Cardioplegic Arrest and Cardiopulmonary Bypass

“…[2][3][4][5][6][7][8] The expression and activation of MAPKs are also altered in the setting of hyperglycemia and diabetes in several animal models. [9][10][11][12][13][14] Recent studies in our laboratory demonstrated that PKC-alpha and PKC-beta are upregulated and activated in the human diabetic (type 2) myocardium in the setting of CP/CPB. [15][16][17][18][19][20][21] Whether diabetes, particularly if combining with CP/CPB and cardiac surgery, further affects MAPKs signaling in the human myocardium has not been investigated.…”

Induction of Proteasome Subunit Low Molecular Weight Protein (LMP)-2 Is Required to Induce Active Remodeling in Adult Rat Ventricular Cardiomyocytes

“…In the past, a focus has been set on the reformation of sarcomeres, while the initiation of this process, namely the degradation of existing sarcomeres, has achieved less attention. We have previously shown that during the cultivation process, an increased expression of p38 MAP kinase occurs [ 31 ]. Activation of p38 MAP kinase drives embryonic stem cells into cardiomyocyte-specific differentiation by enhancing the transcription of myocyte enhancer factor 2C, a transcription factor required for cell differentiation [ 32 , 33 ].…”

Interleukin-6 Contributes to the Paracrine Effects of Cardiospheres Cultured from Human, Murine and Rat Hearts

“…Cell contraction was analyzed as described previously using a cell‐edge detection system at a frequency of 0.5 Hz (Wenzel et al, ). Cells were incubated for 24 h with (1) pure and conditioned medium from human, murine, and rat CDCs, (2) with Il‑6 (100 pg/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, or 1 μg/ml) (3) with pure and conditioned media from human CDCs derived from both a hypertensive and a normotensive donor and a specific antibody against Il‑6 in a dilution of 1/400 as recommended by the manufacturer in the product’s datasheet (Abcam®, Cambridge, UK, rabbit polyclonal) (4) the antibody alone and (5) pure and conditioned media from Il‑6 −/− and Il‑6 +/+ mice.…”