Butyrate prevents muscle atrophy after sciatic nerve crush.
BACKGROUND
Histone deacetylases (HDACs) have been implicated in neurogenic muscle atrophy, but the mechanisms by which HDAC inhibitors might have beneficial effects are not defined.


METHODS
We used sciatic nerve crush to determine the effect of butyrate on denervation-induced gene expression and oxidative stress.


RESULTS
Butyrate treatment initiated 3 weeks before injury and continued 1 week after injury increases histone acetylation and reduces muscle atrophy after nerve crush. Butyrate delivered only after nerve crush similarly prevented muscle atrophy. Butyrate had no effect on the increase in histone deacetylase 4 (HDAC4) protein levels following nerve crush but prevented the increase in expression of myogenin, MuRF1, and atrogin-1. Butyrate did not affect mitochondrial reactive oxygen species production, but it increased antioxidant enzyme activity, reduced proteasome activity, and reduced oxidative damage following nerve injury.


CONCLUSIONS
These data suggest that HDAC inhibitors are promising pharmacological agents for treating neurogenic muscle atrophy. Muscle Nerve 52: 859-868, 2015.
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.|Barshop Institute for Longevity and Aging Studies, San Antonio, Texas, USA.
Michael E
http://orcid.org/0000-0002-0629-0542
ME
Walsh
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.|Barshop Institute for Longevity and Aging Studies, San Antonio, Texas, USA.
Arunabh
A
Bhattacharya
Barshop Institute for Longevity and Aging Studies, San Antonio, Texas, USA.
Yuhong
Y
Liu
Free Radical Biology and Aging Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma, 73104, USA.
Holly
H
Van Remmen
D000818:Animals; D020148:Butyric Acid / Q000627:therapeutic use*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
D020148:Butyric Acid
histone deacetylase; muscle atrophy; myogenin; oxidative stress