The Calcineurin Antagonist, RCAN1-4 is Induced by Exhaustive Exercise in Rat Skeletal Muscle

International audienceThe aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress

État des lieux de la démographie des chirurgiens-dentistes et des zones sous-dotées en Bretagne Occidentale : étude préliminaire pour une enquête nationale, destinée aux étudiants de 6e année

Dans certains territoires nationaux, nous constatons un accès défavorable aux soins buccodentaires. Cette observation est en partie due à la répartition assez hétérogène des Chirurgiens-Dentistes (CD) en France. L’objet de ce travail de thèse est de faire une étude démographique des CD dans les trois départements des Côtes-d’Armor, du Morbihan et du Finistère. Cette étude permettra dans un premier temps, de présenter les zones sous-dotées en CD de ces trois départements aux étudiants d’Odontologie de l’Université de Bretagne Occidentale (UBO). Ensuite, à l’aide d’un questionnaire unique pour toutes les facultés d’Odontologie de France, nous étudierons les réponses des étudiants en troisième cycle d’études Odontologiques, pour déterminer les éléments susceptibles d’empêcher, de motiver, voire de limiter l’installation dans ces zones. Ces résultats vont également alimenter l’enquête nationale concernant les projets d’installation des jeunes diplômés

Pharmacological optimization of Etoposide by Allyl isothiocyanate (AITC) in prostate cancer

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OxidativeResponsive Protein RCAN 1-4 Is Modulated By Acute Exercise In Rat Skeletal Muscles

International audienceRegulator of Calcineurin1 isoform 4 (RCAN1-4)is an oxidative responsive endogenous intracellular phosphatase that inhibits Calcineurin (Cn). Cnis a ubiquitously expressed serine/threonine protein phosphatase under the control of calcium/calmodulin which has been identified in skeletal muscles. However, so far, RCAN1 expression has never been studied under acute exercise. Experiment: 24 Wistar ratswere grouped in three and were subjected to the same physical exercise protocoland then sacrificed either immediately, or 3 hours or 6 hours after exercise. A control group of 8 rats were sacrificed in the same condition. Three different skeletal muscles were collected: Soleus, a predominantly slow twitch muscle rich in type 1 fibers; Extensor DigitorumLongus (EDL), a fast twitch muscle rich in type 2 fibers; andGastrocnemius a ‘mixed muscle’ which contains both type 1 and type 2 fibers. Results: RCAN1-4 was expressed differently in the three muscles. The content of RCAN1-4 was highest in Soleus and remains unchanged after exercise, However RCAN1-4 increased significantly after exercise until 6 hours in EDL and Gastrocnemius. Expression of Cn decreased in all muscles after exercise. PGC-1? as a marker for mitochondrial biogenesis was assayed, although its expression does not significantly changes in any muscle, but it is more expressed in Soleus. Insight in protein and lipid peroxidation showsdifferent patterns of peroxidation of biomolecule in different muscles. Generally malondialdehydeaugments in all muscles after the exercise; however the level of protein carbonyl content increasedonly in EDL and Gastrocnemius but not in Soleus. Conclusion: Acute exercise up-regulated RCAN1-4 expression in rat EDL and Gastrocnemius. Exhaustive exercise is known to induce oxidative stressand RCAN1-4 induction has been shown to help protect against oxidative stress in other tissues. We propose that RCAN1-4 expression represents an important component of the physiological adaptation to exercise and presently we are conducting more investigation using Diabetes Mellitus and Alzheimer’s disease models

Exhaustive exercice modulates expression of Rcan1-4 more than other Rcan1 isoforms in rat skeletal muscle.

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Effect of physical exercise on RCAN1 expression in rat skeletal muscles

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Streptozotocin induced diabetes alone or in combination with exercise does not affect rcan 1 in rat skeletal muscles.

International audienceRegulator of Calcineurin1 (RCAN1) is a calcineurin modulator protein. Calcineurin is ubiquitously expressed Sr/Thr phosphatase under the control of calcium/calmodulin which has been identified in skeletal muscles. Thus far, RCAN1, being an oxidative and high-glucose responsive element, has not been studied under conditions of diabetes and physical exercise. Experiment: 16male Wistar rats received intraperitoneal streptozotocin injection while 16 other were kept as control. Once diabetic state was confirmed, each group was divided into two sub-groups of trained and non-trained. The training consisted of an 8 weeks of treadmill exercise (10° incline, up to 25 mmin-1, 60min/day, 70% VO2). Three different skeletal muscles were collected: Soleus, a predominantly slow twitch muscle rich in type 1 fibers; Extensor Digitorum Longus (EDL), a fast twitch muscle rich in type 2 fibers; and Gastrocnemius a ‘mixed muscle’ which contains both type 1 and 2 fibers. Results: Muscle atrophy and hyperglycemia were confirmed in diabetic rats. Calcineurin, PGC1-alpha and three main RCAN1 isoforms namely; RCAN 1-1L, RCAN1-1S and RCAN1-4 were detected in the three muscles. Neither of them has been modified following the treatments. Diabetes did not modified protein carbonyls in the muscles and TBARS augmented only in soleus after diabetes induction. Conclusion: The streptozotocin induced diabetes and the exercise protocol were not strong enough to bring about an oxidative stress in the muscles, therefore RCAN1 expression was not altered. Our findings are consistent with the previews studies, showing that stress can modulate RCAN1 expression and in the absence of stress RCAN1 remains unchanged