U. Ruegg | Université de Genève (original) (raw)

Papers by U. Ruegg

Journal of Biological Chemistry

International Journal of Molecular Sciences

Intracellular signaling pathways, including the mammalian target of rapamycin (mTOR) and the mito... more Intracellular signaling pathways, including the mammalian target of rapamycin (mTOR) and the mitogen-activated protein kinase (MAPK) pathway, are activated by exercise, and promote skeletal muscle hypertrophy. However, the mechanisms by which these pathways are activated by physiological stimulation are not fully understood. Here we show that extracellular ATP activates these pathways by increasing intracellular Ca2+ levels ([Ca2+]i), and promotes muscle hypertrophy. [Ca2+]i in skeletal muscle was transiently increased after exercise. Treatment with ATP induced the increase in [Ca2+]i through the P2Y2 receptor/inositol 1,4,5-trisphosphate receptor pathway, and subsequent activation of mTOR in vitro. In addition, the ATP-induced increase in [Ca2+]i coordinately activated Erk1/2, p38 MAPK and mTOR that upregulated translation of JunB and interleukin-6. ATP also induced an increase in [Ca2+]i in isolated soleus muscle fibers, but not in extensor digitorum longus muscle fibers. Furtherm...

Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology

Expression of channel protein Orai-1 has been demonstrated in cultured skeletal myoblasts and myo... more Expression of channel protein Orai-1 has been demonstrated in cultured skeletal myoblasts and myotubes. In order to evaluate its functional role in Ca 2+ transport in these cells we used small interfering RNA (siRNA) targeted against mRNA coding for Orai-1. Optimal conditions for the effective transfection of myoblasts and myotubes were found. In experiments using myotubes from an mdx cell line we have shown that inactivation of mRNA coding Orai-1 results in complete suppression of 45 Ca 2+ entry induced by thapsigargin, an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca 2+-ATPase. The data obtained indicate that Orai-1 is involved in store-activated Ca 2+ entry into skeletal myotubes.

Neuromuscular Disorders, 2016

Journal of Neuromuscular Diseases, 2015

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the gene coding for dystrophin and le... more Duchenne Muscular Dystrophy (DMD) is caused by mutations in the gene coding for dystrophin and leads to muscle degeneration, wheelchair dependence and death by cardiac or respiratory failure. Physical exercise has been proposed as a palliative therapy for DMD to maintain muscle strength and prevent contractures for as long as possible. However, its practice remains controversial because the benefits of training may be counteracted by muscle overuse and damage. The effects of physical exercise have been investigated in muscles of dystrophin-deficient mdx mice and in patients with DMD. However, a lack of uniformity among protocols limits comparability between studies and translatability of results from animals to humans. In the present review, we summarize and discuss published protocols used to investigate the effects of physical exercise on mdx mice and DMD patients, with the objectives of improving comparability between studies and identifying future research directions.

Antimicrobial Agents and Chemotherapy, 2008

Frontiers in Physiology, 2015

and Dorchies OM (2015) Caloric restriction induces energy-sparing alterations in skeletal muscle ... more and Dorchies OM (2015) Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding. Front. Physiol. 6:254.

Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, 2009

Neuromuscular Disorders, 2015

In Duchenne muscular dystrophy (DMD) dysregulation of cytosolic calcium appears to be involved in... more In Duchenne muscular dystrophy (DMD) dysregulation of cytosolic calcium appears to be involved in the degeneration of skeletal muscle fibres. Therefore, we have studied the regulation of the free cytosolic calcium concentration ([Ca2+]) under specific stress conditions in cultured myotubes isolated from the hind limbs of wild-type (C57BL10) and dystrophin-deficient mutant mdx mice. [Ca2+]c in the myotubes was estimated by the use of the Ca2'-sensitive fluorescent dye, fura-2. 2 Resting [Ca2+]c was similar in mdx and normal myotubes (35+9 nM and 38 + 11 nM, respectively). However, when mdx myotubes were exposed to a high extracellular calcium concentration ([Ca2+]e) of 40 mm, the [Ca2+]c was elevated to 84 + 29 nm, compared to 49 + 7 nM in normal myotubes. 3 Lowering the osmolarity of the superfusion solution from 300 mOsm to 100 mOsm resulted also in a rise in [Ca2+]r which was about two times higher for mdx (243 + 65 nM) than for C57BL1O (135 + 37 nM). Replacing extracellular Ca2+ by EGTA (0.2 mM) prevented the rise in [Ca2+]c in both mdx and normal myotubes when exposed to the low osmolarity solution. 4 Gadolinium ion (50 guM), an inhibitor of Ca2+ entry, antagonized the rise in [Ca2+]c of myotubes superfused with 40 mM [Ca2+]e by 20-40% for both mdx and C57BL1O cells, but did not significantly reduce the rise in [Ca2+]c when the cells were exposed to the hypo-osmotic buffer (100 mOsm). 5 Incubation of the cell culture for 3-5 days from the onset of induction of myotube formation with the membrane permeable protease inhibitor, calpeptin (50 gM) abolished the rise in [Ca2+]c in mdx myotubes upon exposure to hypo-osmotic shock. 6 Treatment of the cell culture for 3-5 days with ac-methylprednisolone (PDN, 10 guM) attenuated the rise in [Ca2+]c following hypo-osmotic stress for both normal and mdx myotubes by about 50%. 7 The results described here suggest an increased permeability of mdx myotubes to Ca2+ under specific stress conditions. The ameliorating effect of PDN on [Ca2+]c could explain, at least partly, the beneficial effect of this drug on DMD patients.

The Biochemical journal, 1973

The American journal of clinical nutrition, 2002

Duchenne muscular dystrophy is a severe X-linked congenital disorder characterized by lethal musc... more Duchenne muscular dystrophy is a severe X-linked congenital disorder characterized by lethal muscle wasting caused by the absence of the structural protein dystrophin. Because generation of reactive oxygen species appears to play an important role in the pathogenesis of this disease, we tested whether antioxidant green tea extract could diminish muscle necrosis in the mdx mouse dystrophy model. A diet supplemented with 0.01% or 0.05% green tea extract was fed to dams and neonates for 4 wk beginning on the day of birth. Muscle necrosis and regeneration were determined in stained cryosections of soleus and elongator digitorum longus muscles. Radical scavenging by green tea extract was determined in differentiated cultured C2C12 cells treated with tert-butylhydroperoxide, with the use of 2',7'-dichlorofluorescin diacetate as a radical detector. This feeding regimen significantly and dose-dependently reduced necrosis in the fast-twitch muscle elongator digitorum longus but at th...

Journal of muscle research and cell motility, 2001

The pathogenesis of Duchenne muscular dystrophy (DMD), characterised by lack of the cytoskeletal ... more The pathogenesis of Duchenne muscular dystrophy (DMD), characterised by lack of the cytoskeletal protein dystrophin, is not completely understood. An early event in the degenerative process of DMD muscle could be a rise in cytosolic calcium concentration. In order to investigate whether this leads to alterations of contractile behaviour, we studied the excitability and contractile properties of cultured myotubes from control (C57BL/10) and mdx mice, an animal model for DMD. The myotubes were stimulated electrically and their motion was recorded photometrically. No significant differences were found between control and mdx myotubes with respect to the following parameters: chronaxy and rheobase (0.33 +/- 0.03 ms and 23 +/- 4 V vs. 0.39 +/- 0.07 ms and 22 +/- 2 V for C57 and mdx myotubes, respectively), tetanisation frequency (a similar distribution pattern was found between 5 and 30 Hz), fatigue during tetanus (found in 35% of both types of myotubes) and post-tetanic contracture. In ...

The American journal of physiology, 1989

ATP stimulated 45Ca2+ influx in rat aortic smooth muscle cells in a concentration-dependent manne... more ATP stimulated 45Ca2+ influx in rat aortic smooth muscle cells in a concentration-dependent manner (EC50 = 3.6 +/- 0.5 X 10(-7) M). ADP and GTP were less effective than ATP in stimulating 45Ca2+ influx; AMP was weakly active and the adenosine agonist 5'-(N-ethyl-carboxamido)-adenosine (NECA) had no effect. ATP gamma S was about equieffective with ATP, whereas alpha,beta-methylene-ATP (APCPP) did not induce 45Ca2+ influx. Stimulation of 45Ca2+ influx by ATP was not abolished by the dihydropyridine Ca2+ channel antagonist darodipine (PY 108-068), which completely blocked depolarization-induced 45Ca2+ influx. Inorganic cations (La3+, Cd2+, Co2+, Ni2+, Mn2+, and Mg2+) were able to inhibit both agonist- and depolarization-induced 45Ca2+ influx. Cd2+, however, was approximately 20 times more selective in blocking K+-stimulated than agonist-stimulated 45Ca2+ influx. These data indicate that ATP-stimulated Ca2+ influx in rat aortic smooth muscle cells is resistant to darodipine but is r...

Advances in biochemical psychopharmacology, 1982