p38 MAPK Participates in Muscle-Specific RING Finger 1-Mediated Atrophy in Cast-Immobilized Rat Gastrocnemius Muscle.

Skeletal muscle atrophy is a common phenomenon during the prolonged muscle disuse caused by cast immobilization, extended aging states, bed rest, space flight, or other factors. However, the cellular mechanisms of the atrophic process are poorly understood. In this study, we investigated the involvement of mitogen-activated protein kinase (MAPK) in the expression of muscle-specific RING finger 1 (MuRF1) during atrophy of the rat gastrocnemius muscle. Histological analysis revealed that cast immobilization induced the atrophy of the gastrocnemius muscle, with diminution of muscle weight and cross-sectional area after 14 days. Cast immobilization significantly elevated the expression of MuRF1 and the phosphorylation of p38 MAPK. The starvation of L6 rat skeletal myoblasts under serum-free conditions induced the phosphorylation of p38 MAPK and the characteristics typical of cast-immobilized gastrocnemius muscle. The expression of MuRF1 was also elevated in serum-starved L6 myoblasts, but was significantly attenuated by SB203580, an inhibitor of p38 MAPK. Changes in the sizes of L6 myoblasts in response to starvation were also reversed by their transfection with MuRF1 small interfering RNA or treatment with SB203580. From these results, we suggest that the expression of MuRF1 in cast-immobilized atrophy is regulated by p38 MAPK in rat gastrocnemius muscles.

[1]  D. Gerrard,et al.  Mitogen-activated protein kinase signaling is necessary for the maintenance of skeletal muscle mass. , 2009, American journal of physiology. Cell physiology.

[2]  B. Jeon,et al.  Gene Transfer of Redox Factor-1 Inhibits Neointimal Formation: Involvement of Platelet-Derived Growth Factor-&bgr; Receptor Signaling via the Inhibition of the Reactive Oxygen Species–Mediated Syk Pathway , 2009, Circulation research.

[3]  Y. Matsuki,et al.  Overexpression of the transcriptional coregulator Cited2 protects against glucocorticoid-induced atrophy of C2C12 myotubes. , 2009, Biochemical and biophysical research communications.

[4]  Y. Fujio,et al.  Atrogin-1 ubiquitin ligase is upregulated by doxorubicin via p38-MAP kinase in cardiac myocytes. , 2008, Cardiovascular research.

[5]  David R. Thomas,et al.  Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. , 2007, Clinical nutrition.

[6]  I. Seiliez,et al.  Insulin and amino acid availability regulate atrogin-1 in avian QT6 cells. , 2007, Biochemical and biophysical research communications.

[7]  A. Vincent,et al.  MuSK antibody positive myasthenia gravis plasma modifies MURF-1 expression in C2C12 cultures and mouse muscle in vivo , 2005, Journal of Neuroimmunology.

[8]  G. Nader.  Molecular determinants of skeletal muscle mass: getting the "AKT" together. , 2005, The international journal of biochemistry & cell biology.

[9]  D. Glass,et al.  Skeletal muscle hypertrophy and atrophy signaling pathways. , 2005, The international journal of biochemistry & cell biology.

[10]  Richard T. Lee,et al.  Transgenic Overexpression of Locally Acting Insulin-Like Growth Factor-1 Inhibits Ubiquitin-Mediated Muscle Atrophy in Chronic Left-Ventricular Dysfunction , 2005, Circulation research.

[11]  A. Goldberg,et al.  The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling* , 2005, Journal of Biological Chemistry.

[12]  M. Kaneki,et al.  Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle. , 2005, American journal of physiology. Endocrinology and metabolism.

[13]  F. Booth,et al.  Changes in signalling molecule levels in 10-day hindlimb immobilized rat muscles. , 2005, Acta physiologica Scandinavica.

[14]  M. Rudnicki,et al.  Molecular Mechanisms of Muscle Atrophy , 2004, Cell.

[15]  Cam Patterson,et al.  Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  W. Frontera,et al.  IKKβ/NF-κB Activation Causes Severe Muscle Wasting in Mice , 2004, Cell.

[17]  Marco Sandri,et al.  Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy , 2004, Cell.

[18]  A. Goldberg,et al.  Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  L. Graves,et al.  Phosphorylation of insulin receptor substrate‐1 serine 307 correlates with JNK activity in atrophic skeletal muscle , 2003, FEBS letters.

[20]  P. Hasselgren,et al.  Sepsis upregulates the gene expression of multiple ubiquitin ligases in skeletal muscle. , 2003, The international journal of biochemistry & cell biology.

[21]  C. Gregorio,et al.  Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1 , 2002, The Journal of cell biology.

[22]  Lu Zhou,et al.  NFκB and AP-1 mediate transcriptional responses to oxidative stress in skeletal muscle cells , 2001 .

[23]  A. Goldberg,et al.  Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D J Glass,et al.  Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy , 2001, Science.

[25]  A. Goldberg,et al.  What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? , 2001, Current opinion in clinical nutrition and metabolic care.

[26]  J. Avruch,et al.  Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. , 2001, Physiological reviews.

[27]  K. Pelin,et al.  Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. , 2001, Journal of molecular biology.

[28]  M. Karin,et al.  Mammalian MAP kinase signalling cascades , 2001, Nature.

[29]  P. Freemont.  Ubiquitination: RING for destruction? , 2000, Current Biology.

[30]  A. Goldberg,et al.  Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. , 1995, The Biochemical journal.

[31]  F. Booth,et al.  Molecular and cellular adaptation of muscle in response to exercise: perspectives of various models. , 1991, Physiological reviews.

[32]  A. Samarel,et al.  Protein synthesis and degradation during starvation-induced cardiac atrophy in rabbits. , 1987, Circulation research.

[33]  F. Booth,et al.  Production of rat muscle atrophy by cast fixation. , 1973, Journal of applied physiology.

[34]  K. Won,et al.  p38 mitogen-activated protein kinase contributes to angiotensin II-stimulated migration of rat aortic smooth muscle cells. , 2007, Journal of pharmacological sciences.

[35]  Yi-Ping Li,et al.  TNF- acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle , 2005 .