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

Autor: Brian S. Tseng, Rick E. Rabon, Warren C. McClure, Hirofumi Ogawa
Rok vydání: 2006
Předmět:
musculoskeletal diseases
mdx mouse
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
Amidinotransferases
Arginine
Duchenne muscular dystrophy
Biology
Motor Activity
Creatine
Gene Expression Regulation
Enzymologic
Article
chemistry.chemical_compound
Mice
Downregulation and upregulation
Internal medicine
medicine
Animals
Coloring Agents
Fluorescent Antibody Technique
Indirect
Muscle
Skeletal
Genetics (clinical)
Age Factors
Skeletal muscle
Muscular Dystrophy
Animal
medicine.disease
musculoskeletal system
Up-Regulation
Guanidinoacetate N-methyltransferase
Mice
Inbred C57BL
Muscular Dystrophy
Duchenne
Disease Models
Animal
medicine.anatomical_structure
Endocrinology
Neurology
chemistry
Biochemistry
Pediatrics
Perinatology and Child Health
biology.protein
Mice
Inbred mdx
Guanidinoacetate N-Methyltransferase
Neurology (clinical)
Dystrophin
Energy Metabolism
Evans Blue
Zdroj: Neuromuscular disorders : NMD. 17(8)
ISSN: 0960-8966
Popis: 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.
Databáze: OpenAIRE
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