Meltzer, M., Long, K., Nie, Y., Gupta, M. , Yang, J. and Montano, M. (2010) The RNA editor gene ADAR1 is induced in myoblasts by inflammatory ligands and buffers stress response. Clinical and Translational Science, 3(3), pp. 73-80. (doi: 10.1111/j.1752-8062.2010.00199.x)
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Abstract
Muscle atrophy remains a significant concern in multiple inflammatory conditions, including injury, sepsis, cachexia, and HIV-associated wasting. Herein, we show that inflammatory stressors, including TNF-alpha, IFN-gamma, or lipopolysaccharide, potently induced the novel expression of the RNA editor ADAR1, an observation not previously described in muscle cells. We also observed that cytokine stimulation suppressed muscle-associated microRNAs, an observation also not previously demonstrated. To map potential effects of ADAR1 induction in the muscle program, we conducted knockdown and overexpression studies in the mouse C2C12 muscle precursor cell (MPC) line and in primary human MPCs. We show that knockdown of stress-induced ADAR1 increased inflammation-mediated declines in the muscle differentiation markers Myogenin and myosin heavy chain, and knockdown reduced levels of active phosphorylated Akt (phospho-Akt), but had no effect on microRNA transcript levels, suggesting a role for ADAR1 in buffering inflammatory stress effects on myogenic transcription and protein synthesis pathways. In addition, overexpression of recombinant ADAR1 suppressed active phosphorylated double-stranded RNA (dsRNA)-dependent protein kinase (phospho-PKR), consistent with a role for ADAR1 in limiting inflammation-driven catabolic atrophy pathways. Collectively, these data identify a novel regulatory role for ADAR1 activation under inflammatory stress to both promote muscle protein synthesis pathways and limit atrophy pathways.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Gupta, Professor Mayetri |
| Authors: | Meltzer, M., Long, K., Nie, Y., Gupta, M., Yang, J., and Montano, M. |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| College/School: | College of Science and Engineering > School of Mathematics and Statistics > Statistics |
| Journal Name: | Clinical and Translational Science |
| ISSN: | 1752-8054 |
| ISSN (Online): | 1752-8062 |
| Published Online: | 25 June 2010 |
| Related URLs: |
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