Myostatin - Signaling pathways weigh in on decisions to make or break skeletal muscle

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Research Abstract from Curr Opin Clin Nutr Metab Care. 2004

Jul;7(4):443-450.

Signaling pathways weigh in on decisions to make or break skeletal

muscle.

(mentions Myostatin)

Guttridge DC.

Division of Human Cancer Genetics, The Ohio State University, Columbus,

Ohio, USA.

PURPOSE OF REVIEW: Regulation of muscle size is essential for proper

development and homeostasis of adult musculature. This regulation is

mediated in large part by signal transduction pathways that promote the

synthesis or breakdown of skeletal muscle. PI(3)K/Akt, myostatin and

NF-kappaB represent three such pathways that will be the focus of this

review.

RECENT FINDINGS: Recent reports solidify the requirement of the

PI(3)K/Akt pathway in the regulation of muscle hypertrophy. In response

to IGF-1, Akt activates downstream effectors, mTOR and p70S6K to

stimulate protein synthesis thereby increasing the cytoplasmic

compartment in muscle fibers. Tsc2 was also identified as a novel Akt

target, whose phosphorylation and inactivation by Akt may lead to an

increase in cell size. The mechanisms by which myostatin functions in

muscle wasting was recently explored using in-vitro assays of

myogenesis. Myostatin was found to repress myogenesis by inhibiting the

synthesis and activity of MyoD. Paradoxically, myostatin expression is

itself regulated by MyoD binding to the myostatin promoter. The

NF-kappaB transcription factor also functions as a negative regulator of

myogenesis by inhibiting MyoD. Chronic activation of NF-kappaB has been

associated with muscle wasting, but the mechanisms by which this

regulation occurs remain for the most part unknown.

SUMMARY: Recent cell culture and animal studies have provided insight on

the mechanisms by which Akt, myostatin, and NF-kappaB signaling pathways

regulate muscle size. Clinical intervention to boost Akt signaling or

modulate myostatin and NF-kappaB activities may prove useful in diseases

associated with chronic muscle wasting.