Specialization of mitochondrial and vascular oxidant modulated VEGFR in the denervated skeletal muscle
Autor: | Pei-Yan Huang, Hui Zhao, Jun-Guo Wu, Han-Wei Huang |
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Rok vydání: | 2013 |
Předmět: |
Male
Xanthine Oxidase medicine.medical_specialty Interleukin-1beta Cell Neuromuscular Junction Inflammation Mitochondrion Biology Rats Sprague-Dawley Internal medicine medicine Animals Receptors Cholinergic Muscle Skeletal Interleukin-15 Protein Tyrosine Phosphatase Non-Receptor Type 1 Denervation Muscle Denervation Vascular Endothelial Growth Factor Receptor-1 Receptor Protein-Tyrosine Kinases Skeletal muscle Cell Biology Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Sciatic Nerve Vascular Endothelial Growth Factor Receptor-2 Muscle atrophy Mitochondria Rats Endocrinology medicine.anatomical_structure Gene Expression Regulation Mitochondrial biogenesis medicine.symptom Signal Transduction Transcription Factors |
Zdroj: | Cellular Signalling. 25:2106-2114 |
ISSN: | 0898-6568 |
DOI: | 10.1016/j.cellsig.2013.06.014 |
Popis: | Denervation of skeletal muscles results in timely muscular inflammation and muscle-T cell interaction, the cellular events might orchestrate a local circuit involved with IL-1β and IL-15. In the present study, by a combination assay of nerve-muscle preparation, western blot, immuno-precipitation, and radioactive of enzyme activity, we confirmed that mitochondrial and vascular oxidants were considerably up-regulated following gastrocnemius denervation, which was due to gradual decay in mitochondrial biogenesis and XO pathway and accompanied by strengthened IL-1β-VEGFR-2 and IL-15-VEGFR-1 signaling. Intriguingly, these alterations could be triggered by the early established muscular inflammation. In contrast, with prolonged muscle denervation, settings of organelle interconnection were ultimately conveyed by ER bound PTP1B, which promoted VEGFR-1 signaling and contributed to VEGFR-2 activation, and the process could be modulated by mitochondrial and vascular oxidant. Importantly, VEGFR-2 could rescue the disruption of MuSK activity and AchR cluster exerted by IL-1β and IL-15, with PGC-1α and XO involvement. Altogether, extensive network centered on VEGFR-2 signaling was essentially contributed to early recovery processes regarding muscle denervation. Increasing knowledge of this mechanism might open up a conduit for functional response to muscle atrophy, and enable the development of better agents to combat the related disorders. |
Databáze: | OpenAIRE |
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