2013 OSU Molecular Life Sciences
Interdisciplinary Graduate Programs Symposium

 

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Poster number 7 submitted by Meghna Pant

The role of increased Sarcolipin expression in neonatal development and in muscle disease

Meghna Pant (physiology and cell biology, The Ohio state university), Naresh C. Bal (physiology and cell biology, The Ohio state university), Dawn A. Delfin (Molecular and cellular Biochemistry, The Ohio state university), Jill Rafael-Fortney (Molecular and cellular Biochemistry, The Ohio state university), Muthu Periasamy (physiology and cell biology, The Ohio state university)

Abstract:
Skeletal muscle constitutes more than 40% of body mass and has been suggested to play an important role in thermogenesis and metabolism. Studies in our laboratory have shown that Sarcolipin (SLN) (31 amino acid trans-membrane peptide) an inhibitor of SR Ca2+ ATP ase (SERCA) is critical for muscle-based thermogenesis. Therefore we investigated the importance of SLN during early mouse neonatal development and in dystrophic muscle. We found that SLN expression is several fold higher at birth in most skeletal muscles studied, which then gradually decreases in adult fast twitch skeletal muscles but preserved in oxidative/slow twitch fibers. Gradual cold acclimatization of these neonatal mice extended the duration of SLN expression in all the muscles. We also observed that in SLN KO neonates the expression of key metabolic regulators involved in fatty acid and glucose oxidation were altered. When compared to skeletal muscle from dystrophic MDX mice, SLN expression was significantly upregulated in the utrophin-dystrophin double knock out (DKO) mice. Interestingly, the DKO mice exhibit a higher level of whole body oxygen consumption but they show decreased mobility. These data together suggest that increased expression of SLN is associated with an increased metabolic rate which is important for maintaining thermogenesis in neonatal stages and an oxidative phenotype in dystrophic muscle.

References:

Bal et. al., Nature Medicine 2012 ;18, 1575-9
Block BA. Thermogenesis in muscle. Annu Rev Physiol. 1994;56:535-577
Mall, S. et al., (2006), J Biol Chem 281, 36597-36602.
Babu GJ et al., Proc Natl Acad Sci U S A. 2007;104:17867-17872
Babu GJ et al., J Mol Cell Cardiol. 2007;43:215-222
Anne E. Deconinck, Jill A. Rafael, et al.,. Cell, Vol. 90, 717–727, August 22, 1997,

Keywords: sarcolipin, metabolism, muscle dystrophy