Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice.

Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Research Abstract Details 

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Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Abstract Text:

Warren C McClure,Rick E Rabon,Hirofumi Ogawa,Brian S Tseng,

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular human disease caused by dystrophin deficiency. The mdx mouse lacks dystrophin protein, yet does not exhibit the debilitating DMD phenotype. Investigating compensatory mechanisms in the mdx mouse may shed new insights into modifying DMD pathogenesis. This study targets two metabolic genes, guanidinoacetate methyltransferase (GAMT) and arginine:glycine amidinotransferase (AGAT) which are required for creatine synthesis. We show that GAMT and AGAT mRNA are up-regulated 5.4- and 1.9-fold respectively in adult mdx muscle compared to C57. In addition, GAMT protein expression is up-regulated at least 2.5-fold in five different muscles of mdx vs. control. Furthermore, we find GAMT immunoreactivity in up to 80% of mature mdx muscle fibers in addition to small regenerating fibers and rare revertants; while GAMT immunoreactivity is equal to background levels in all muscle fibers of mature C57 mice. The up-regulation of the creatine synthetic pathway may help maintain muscle creatine levels and limit cellular energy failure in leaky mdx skeletal muscles. These results may help better understand the mild phenotype of the mdx mouse and may offer new treatment horizons for DMD.

Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Publishing Authors By Initials

WC McClure,RE Rabon,H Ogawa,BS Tseng,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Neuromuscular disorders : NMD

VOLUME: 17

Page Numbers: 639-50

Journal Abbreviation: Neuromuscul. Disord.

ISSN: 0960-8966

DAY: 27

MONTH: 06

YEAR: 2007

Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9111470

Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: physiology

Chemical & Substance for Abstract: Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice. Information

Substance Name: glycine amidinotransferase

Registry Number: EC 2.1.4.1

Grant and Affiliation Information for Upregulation of the creatine synthetic pathway in skeletal muscles of mature mdx mice.

AFFILIATION: Department of Pediatrics, University of Colorado-Denver Health Science Center, The Children's Hospital Fitzsimons Campus, Aurora, CO 80045, USA.

Country: England

AGENCY: United States NIDDK

GRANT: P30 DK 57516

ACRONYM: DK

MEDLINETA: Neuromuscul Disord

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