A5020744253- Muscle metabolism and nutrition
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Advanced MRI Techniques and Applications
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Metabolism, Diabetes, and Cancer
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Ion channel regulation and function
- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Diet and metabolism studies
- Pancreatic function and diabetes
- Exercise and Physiological Responses
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Cardiovascular Function and Risk Factors
- Chemotherapy-induced cardiotoxicity and mitigation
- Biotin and Related Studies
- Cardiovascular and exercise physiology
- Protein Structure and Dynamics
- Coenzyme Q10 studies and effects
- Force Microscopy Techniques and Applications
ETH Zurich
2011-2024
Board of the Swiss Federal Institutes of Technology
1983-2021
École Polytechnique Fédérale de Lausanne
2000-2016
Institute of Cell Biology
1991-2011
Laboratory of Fundamental and Applied Bioenergetics
2007
University of Zurich
2007
Université Joseph Fourier
2007
Inserm
2007
Dartmouth College
2005
Yale University
1986-2005
AMP-activated protein kinase (AMPK) is a heterotrimeric that crucial for cellular energy homeostasis of eukaryotic cells and organisms. Here we report on the activation AMPK alpha1beta1gamma1 alpha2beta2gamma1 by their upstream kinases (Ca(2+)/calmodulin-dependent kinase-beta LKB1-MO25alpha-STRADalpha), deactivation phosphatase 2Calpha, extent stimulation its allosteric activator AMP, using purified recombinant enzyme preparations. An accurate high pressure liquid chromatography-based method...
Previous studies showed that insulin antagonizes AMP-activated protein kinase activation by ischemia and B might be implicated. Here we investigated whether the direct phosphorylation of participate in this effect. Protein phosphorylated recombinant bacterially expressed heterotrimers at Ser(485) alpha1-subunits. In perfused rat hearts, alpha1/alpha2 subunits on Ser(485)/Ser(491) was increased pretreatment decreased alpha-subunits Thr(172) a subsequent ischemic episode. It is proposed effect...
AMP-activated protein kinase (AMPK) is a heterotrimeric that regulates glucose transport mediated by cellular stress or pharmacological agonists such as 5-aminoimidazole-4-carboxamide 1 β-d-ribonucleoside (AICAR). AS160, Rab GTPase-activating protein, provides mechanism linking AMPK signaling to uptake. We show AICAR increases AMPK, acetyl-CoA carboxylase, and AS160 phosphorylation insulin-independent mechanisms in isolated skeletal muscle. Recombinant complexes (α1β1γ1 α2β2γ1) phosphorylate...
Cyclosporin A sensitive swelling of mitochondria isolated from control mouse livers and the transgenic mice expressing human ubiquitous mitochondrial creatine kinase occurred in presence both 40 μM calcium 5 atractyloside which was accompanied by a 2.5‐fold increase over state 4 respiration rates. Creatine cyclocreatine inhibited latter only liver mitochondria. Protein complexes detergent solubilised rat brain extracts, containing octameric kinase, porin adenine nucleotide translocator, were...
Published information on the properties of two proteins from chicken muscle, creatine kinase (MM-creatine kinase) and an M-line protein, suggested that they might be identical molecules. Different published procedures were used to purify homogeneity, preparations compared. Creatine specific activity increased during purification reaching a value comparable purified MM-creatine kinase. The migrated identically in electrophoretic systems and, after electrophoresis, both could stained for...
Abstract: The loss of ATP, which is needed for ionic homeostasis, an early event in the neurotoxicity glutamate and β‐amyloid (Aβ). We hypothesize that cells supplemented with precursor creatine make more phosphocreatine (PCr) create large energy reserves consequent neuroprotection against stressors. In serum‐free cultures, at 0.5‐1 m M was toxic to embryonic hippocampal neurons. Creatine >0.1 greatly reduced toxicity. (1 ) could be added as late 2 h after achieve protection 24 h....
Mitochondria from transgenic mice, expressing enzymatically active mitochondrial creatine kinase in liver, were analyzed for opening of the permeability transition pore absence and presence substrates but with no external adenine nucleotides added. In mitochondria these cyclosporin A-inhibited was delayed by or cyclocreatine not beta-guanidinopropionic acid. This observation correlated ability to stimulate state 3 respiration extramitochondrial ATP. The dependence on calcium magnesium...
Highly purified fractions of sarcoplasmic reticulum (SR) were prepared from chicken pectoralis muscles (Saito, A., Seiler, S., Chu, and Fleischer, S. (1984) J. Cell Biol. 99, 875-885) analyzed for the presence creatine kinase (CK). Vesicles derived longitudinal SR contained 0.703 +/- 0.428 IU CK/mg protein. Immunogold localization muscle-type MM-CK on ultrathin cryosections muscle, after removal soluble CK, revealed relatively strong in situ labeling M-CK remaining bound to M band as well...
OBJECTIVE— Emerging evidence suggests that dietary phytoestrogens can have beneficial effects on obesity and diabetes, although their mode of action is not known. Here, we investigate the mechanisms mediating lipid glucose metabolism in rodents. RESEARCH DESIGN AND METHODS— Male CD-1 mice were fed from conception to adulthood with either a high soy–containing diet or soy-free diet. Serum levels circulating isoflavones, ghrelin, leptin, free fatty acids, triglycerides, cholesterol quantified....
The reaction of peroxynitrite (PN) with sarcomeric mitochondrial creatine kinase (Mi<sub>b</sub>-CK; EC2.7.3.2) was observed at different stages complexity (i) purified Mi-CK, (ii) enzyme bound on isolated mitoplasts, and (iii) within intact respiring mitochondria. Creatine-stimulated respiration abolished by PN concentrations likely to be physiological far before the respiratory chain itself affected, thus demonstrating that Mi-CK is a prime target for inactivation in reversed 22%...
After 10 wash cycles, 0.8 u.e. of creatine kinase activity remained bound per mg chicken pectoralis myofibrils which had been freed soluble kinase, mitochondria, and membranes. The is located at the M-band contributes to electron density this sarcomeric structure (Wallimann, T., Pelloni, G.W., Turner, D.C., Eppenberger, H. M. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 4296-4300). By measuring combined actin-activated Mg2+-ATPase reactions by pH-stat, it was shown that amount M-line-bound...
Abstract The mitochondrial isoform of creatine kinase (Mi-CK, EC 2.7.3.2) purified to homogeneity from chicken cardiac muscle by the mild and efficient technique described in this article was greater than or equal 99.5% pure consisted 95% a distinct, octameric Mi-CK protein species, with Mr 364,000 +/- 30,000 an apparent subunit 42,000. remaining 5% were dimeric 86,000 8,000. Octamerization not due covalent linkages intermolecular disulfide bonding. Upon dilution into buffers low ionic...