Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of α1-syntrophin and PLC/PKC in SOCE regulation
| Autor: | Aurélien Chatelier, Rania Harisseh, Bruno Constantin, Christophe Magaud, Nadine Déliot |
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| Přispěvatelé: | Institut de Physiologie et Biologie Cellulaires (IPBC), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers |
| Rok vydání: | 2013 |
| Předmět: |
Indoles
Patch-Clamp Techniques ORAI1 Protein Physiology [SDV]Life Sciences [q-bio] Duchenne muscular dystrophy Muscle Fibers Skeletal Gene Expression Muscle Proteins Gadolinium [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] α1-syntrophin Maleimides 0302 clinical medicine human primary myotubes Estrenes Cells Cultured Protein Kinase C Syntrophin 0303 health sciences Myogenesis Chemistry Imidazoles Calcium Channel Blockers Pyrrolidinones Neoplasm Proteins Sarcoplasmic Reticulum SOCE Ca2+/PLC/PKC medicine.medical_specialty Nifedipine Primary Cell Culture TRPV2 TRPV Cation Channels 03 medical and health sciences Internal medicine DMD [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] medicine Humans Calcium Signaling Stromal Interaction Molecule 1 Protein kinase C TRPC Cation Channels 030304 developmental biology Calcium metabolism Calcium-Binding Proteins Membrane Proteins Cell Biology medicine.disease Muscular Dystrophy Duchenne Endocrinology Type C Phospholipases Calcium Channels Calcium influx [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Physiology-Cell Physiology American Journal of Physiology-Cell Physiology, American Physiological Society, 2013, 304 (9), pp.C881-C894. ⟨10.1152/ajpcell.00182.2012⟩ |
| ISSN: | 1522-1563 0363-6143 |
| Popis: | Calcium homeostasis is critical for several vital functions in excitable and nonexcitable cells and has been shown to be impaired in many pathologies including Duchenne muscular dystrophy (DMD). Various studies using murine models showed the implication of calcium entry in the dystrophic phenotype. However, alteration of store-operated calcium entry (SOCE) and transient receptor potential vanilloid 2 (TRPV2)-dependant cation entry has not been investigated yet in human skeletal muscle cells. We pharmacologically characterized basal and store-operated cation entries in primary cultures of myotubes prepared from muscle of normal and DMD patients and found, for the first time, an increased SOCE in DMD myotubes. Moreover, this increase cannot be explained by an over expression of the well-known SOCE actors: TRPC1/4, Orai1, and stromal interaction molecule 1 (STIM1) mRNA and proteins. Thus we investigated the modes of regulation of this cation entry. We firstly demonstrated the important role of the scaffolding protein α1-syntrophin, which regulates SOCE in primary human myotubes through its PDZ domain. We also studied the implication of phospholipase C (PLC) and protein kinase C (PKC) in SOCE and showed that their inhibition restores normal levels of SOCE in DMD human myotubes. In addition, the involvement of TRPV2 in calcium deregulation in DMD human myotubes was explored. We showed an abnormal elevation of TRPV2-dependant cation entry in dystrophic primary human myotubes compared with normal ones. These findings show that calcium homeostasis mishandling in DMD myotubes depends on SOCE under the influence of Ca2+/PLC/PKC pathway and α1-syntrophin regulation as well as on TRPV2-dependant cation influx. |
| Databáze: | OpenAIRE |
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