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Rainer Hambrecht

Publications and source records attributed to Rainer Hambrecht.

60 records · Page 4Linked to original sources
PubMed2002

Induction of iNOS expression in skeletal muscle by IL-1beta and NFkappaB activation: an in vitro and in vivo study.

OBJECTIVE: The intracellular pathway and the regulation of inducible nitric oxide synthase (iNOS) expression in skeletal muscle is incompletely understood. In vitro studies, using different cell types, suggest that inflammatory cytokines are potential triggers to induce iNOS expression. METHODS: To analyze intracellular pathways leading to iNOS induction, rat skeletal myoblasts were incubated with inflammatory cytokines and assessed for iNOS expression by Western blot and Griess reaction. To confirm the in vitro findings, local cytokine levels were determined in skeletal muscle biopsies of patients with chronic heart failure (CHF) and correlated with iNOS expression. RESULTS: Nitrite accumulation in the myoblast culture supernatant or iNOS protein in the cell pellet was significantly increased after incubation with IL-1beta in combination with gamma-IFN. Priming experiments revealed that gamma-IFN elevated the expression of IL-1beta receptor mRNA, whereby IL-1beta was able to induce iNOS expression. The cytokine-mediated iNOS induction was significantly reduced by blocking ERK1/ERK2 activation and completely abolished by the inhibition of NFkappaB. In skeletal muscle biopsies of CHF patients the local content of IL-1beta was significantly increased as compared to healthy controls. Furthermore, a linear correlation between IL-1beta content and iNOS expression in the skeletal muscle was detected. CONCLUSIONS: These data demonstrate that IL-1beta, together with the priming effect of gamma-IFN, induces iNOS expression in skeletal muscle via activation of ERK1/ERK2 and NFkappaB.

Aged↗
PubMed2002

Chronic heart failure and skeletal muscle catabolism: effects of exercise training.

Although the clinical picture of cardiac cachexia is well-known in patients with advanced chronic heart failure (CHF) the factors that determine who is at risk for this progressive catabolic syndrome and who is not remain unclear. Different endocrine systems have been accused of being involved in this process: an imbalance between catabolic and anabolic steroids with an elevated cortisol/dihydroepiandrosterone ratio, an increased resting metabolic rate due to high levels of circulating catecholamines, various cytokines are activated in CHF (i.e. TNF-alpha, IL-6, IL-1beta and others), and elevated levels of growth hormone (GH) with inappropriately normal or low serum levels of insulin-like growth factor-I (IGF-I) have been described in cardiac cachexia. These catabolic factors contribute to peripheral muscle atrophy, augment the expression of the inducible nitric oxide synthase (iNOS), which in turn inhibits the aerobic cellular metabolism. The present review examines whether the catabolic factors can be influenced by a classical anabolic intervention: regular physical exercise training. Long-term training programs increase skeletal muscle cytochrome c oxidase activity and are associated with reduced local expression of pro-inflammatory cytokines as well as iNOS, and augment local IGF-I production. In concert, these beneficial effects of exercise training may help to retard the catabolic process in CHF finally leading to cardiac cachexia and death.

Chronic Disease↗
PubMedDate not supplied

Exercise and the coronary circulation-alterations and adaptations in coronary artery disease.

Coronary vasorelaxation depends on nitric oxide (NO) bioavailability, which is a function of endothelial nitric oxide synthase-derived NO production and NO inactivation by reactive oxygen species. This fine-tuned balance is disrupted in coronary artery disease (CAD). The impairment of NO production in conjunction with excessive oxidative stress promotes the loss of endothelial cells by apoptosis, leads to a further aggravation of endothelial dysfunction and triggers myocardial ischemia in CAD. In healthy individuals, increased release of NO from the vasculature in response to exercise training results from changes in endothelial nitric oxide synthase expression, phosphorylation, and conformation. However, exercise training has assumed a role in cardiac rehabilitation of patients with CAD, as well, because it reduces mortality and increases myocardial perfusion. This has been largely attributed to exercise training-mediated correction of coronary endothelial dysfunction in CAD. Indeed, regular physical activity restores the balance between NO production and NO inactivation by reactive oxygen species in CAD, thereby enhancing the vasodilatory capacity in different vascular beds. Because endothelial dysfunction has been identified as a predictor of cardiovascular events, the partial reversal of endothelial dysfunction secondary to exercise training might be the most likely mechanism responsible for the exercise training-induced reduction in cardiovascular morbidity and mortality in patients with CAD.

Coronary Artery Disease↗
PubMedDate not supplied

Differential gene expression in skeletal muscle after induction of heart failure: impact of cytokines on protein phosphatase 2A expression.

Different intrinsic alterations of skeletal muscle metabolism and gene expression have been described in chronic heart failure (CHF). As proposed skeletal muscle alterations in CHF may contribute to exercise intolerance and early muscular fatigue. However the exact molecular changes occurring in the skeletal muscle are still unclear. The aim of this study was to characterize the pattern of differential gene expression in an animal model of CHF and to study the regulation of one selected gene. Rats were subjected to LAD ligation or sham operation. mRNA was isolated from musculus quadriceps of both groups and differential gene expression was determined by subtractive hybridization. Quantitative RT-PCR and cell culture experiments were performed to further characterize the changed expression of protein phosphatase 2A (PP2A) in human skeletal muscle biopsies as well as the cytokine dependent regulation of PP2A expression. Out of 800 picked clones differential expression of 24 distinct genes could be identified by sequencing and reverse Northern blotting. PP2A expression demonstrated a significant upregulation in skeletal muscle biopsies from patients with CHF as compared to healthy controls (9.7 +/- 1.9 vs. 4.2 +/- 0.7 arbitrary units; p<0.05). Incubation of rat skeletal muscle myoblasts with a combination of TNF-alpha, IL-1beta, and gamma-IFN caused a 3-fold upregulation of PP2A expression vs. untreated cells. These results suggest that CHF is accompanied by changes in expression of genes involved in energy metabolism, contractility, and apoptosis in the skeletal muscle. The upregulation of PP2A, an important regulator in intracellular signaling and apoptosis, may be due to an increase of inflammatory cytokines.

Animals↗