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Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats.

Publication ,  Journal Article
Shankaran, M; Shearer, TW; Stimpson, SA; Turner, SM; King, C; Wong, P-YA; Shen, Y; Turnbull, PS; Kramer, F; Clifton, L; Russell, A; Evans, WJ ...
Published in: Am J Physiol Endocrinol Metab
March 15, 2016

Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167-201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated (r(2) = 0.90-0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM.

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Published In

Am J Physiol Endocrinol Metab

DOI

EISSN

1522-1555

Publication Date

March 15, 2016

Volume

310

Issue

6

Start / End Page

E405 / E417

Location

United States

Related Subject Headings

  • Receptors, Androgen
  • Rats, Sprague-Dawley
  • Rats
  • Proteome
  • Protein Biosynthesis
  • Ovariectomy
  • Organ Size
  • Muscle, Skeletal
  • Muscle Proteins
  • Mass Spectrometry
 

Citation

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Shankaran, M., Shearer, T. W., Stimpson, S. A., Turner, S. M., King, C., Wong, P.-Y., … Evans, W. J. (2016). Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats. Am J Physiol Endocrinol Metab, 310(6), E405–E417. https://doi.org/10.1152/ajpendo.00257.2015
Shankaran, Mahalakshmi, Todd W. Shearer, Stephen A. Stimpson, Scott M. Turner, Chelsea King, Po-Yin Anne Wong, Ying Shen, et al. “Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats.Am J Physiol Endocrinol Metab 310, no. 6 (March 15, 2016): E405–17. https://doi.org/10.1152/ajpendo.00257.2015.
Shankaran M, Shearer TW, Stimpson SA, Turner SM, King C, Wong P-YA, et al. Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats. Am J Physiol Endocrinol Metab. 2016 Mar 15;310(6):E405–17.
Shankaran, Mahalakshmi, et al. “Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats.Am J Physiol Endocrinol Metab, vol. 310, no. 6, Mar. 2016, pp. E405–17. Pubmed, doi:10.1152/ajpendo.00257.2015.
Shankaran M, Shearer TW, Stimpson SA, Turner SM, King C, Wong P-YA, Shen Y, Turnbull PS, Kramer F, Clifton L, Russell A, Hellerstein MK, Evans WJ. Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats. Am J Physiol Endocrinol Metab. 2016 Mar 15;310(6):E405–E417.

Published In

Am J Physiol Endocrinol Metab

DOI

EISSN

1522-1555

Publication Date

March 15, 2016

Volume

310

Issue

6

Start / End Page

E405 / E417

Location

United States

Related Subject Headings

  • Receptors, Androgen
  • Rats, Sprague-Dawley
  • Rats
  • Proteome
  • Protein Biosynthesis
  • Ovariectomy
  • Organ Size
  • Muscle, Skeletal
  • Muscle Proteins
  • Mass Spectrometry