Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy
Hijikata Y, Katsuno M, Suzuki K, Hashizume A, Araki A, Yamada S, Inagaki T, Iida M, Noda S, Nakanishi H, Banno H, Mano T, Hirakawa A, Adachi H, Watanabe H, Yamamoto M, Sobue G
Annals of clinical and translational neurology · 34 citas
Cómo se estudió
- Diseño
- Estudio transversal (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Japan Agency for Medical Research and Development
- Gobierno
- Ministry of Education, Culture, Sports, Science and Technology
- Organización sin fines de lucro
- Foundation of Synapse and Neurocircuit Pathology
- Organización sin fines de lucro
- Kanae Foundation for the Promotion of Medical Science
- Gobierno
- Japan Society for the Promotion of Science
- Gobierno
- Japan Science and Technology Agency
- Sin clasificar
- Core Research for Evolutional Science and Technology
- Gobierno
- Ministry of Education, Culture, Sports, Science, and Technology
- Subvenciones
- Japan Agency for Medical Research and Development (15ek0109165); Japan Science and Technology Agency (CREST); Japan Agency for Medical Research and Development (CREST); Ministry of Education, Culture, Sports, Science and Technology (26670439); Japan Society for the Promotion of Science (26670440); Japan Society for the Promotion of Science (26670439); Ministry of Education, Culture, Sports, Science and Technology (15K15337); Ministry of Education, Culture, Sports, Science and Technology (26670440); Ministry of Education, Culture, Sports, Science and Technology (26293206); Ministry of Education, Culture, Sports, Science and Technology (22110005); Japan Society for the Promotion of Science (15K15337); Japan Society for the Promotion of Science (26293206); Japan Society for the Promotion of Science (CREST); Japan Society for the Promotion of Science (26117002); Japan Society for the Promotion of Science (26117001)
Según 8 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2016-06-23 · Ann Clin Transl Neurol · vol. 3 · número 7 · págs. 537–546
- Editorial
- Wiley
- Citado
- 47 citas · más que el 93% de estudios similares · 3.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 44 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY-NC-ND
- Áreas de investigación
- Genetic Neurodegenerative Diseases · Muscle metabolism and nutrition · Amyotrophic Lateral Sclerosis Research
- Palabras clave
- Medicine, Spinal muscular atrophy, Creatine, Muscle contracture, Atrophy, Progressive muscular atrophy, Physical medicine and rehabilitation, Spinal and bulbar muscular atrophy, Muscle atrophy, Physical therapy, Pathology, Anatomy, Internal medicine, Amyotrophic lateral sclerosis, Disease
17 autores
- Yasuhiro Hijikata🇯🇵Nagoya University
- Masahisa Katsuno🇯🇵 · autor de correspondenciaNagoya University
- Keisuke Suzuki🇯🇵National Center for Geriatrics and Gerontology; Nagoya University
- Atsushi Hashizume🇯🇵Nagoya University
- Amane Araki🇯🇵Nagoya University
- Shinichiro Yamada🇯🇵Nagoya University
- Tomonori Inagaki🇯🇵Nagoya University
- Madoka Iida🇯🇵Nagoya University
- Seiya Noda🇯🇵Nagoya University
- Hirotaka Nakanishi🇯🇵Nagoya University
- Haruhiko Banno🇯🇵Nagoya University Hospital; Nagoya University
- Tomoo Mano🇯🇵Nagoya University
- Akihiro Hirakawa🇯🇵Nagoya University
- Hiroaki Adachi🇯🇵University of Occupational and Environmental Health Japan; Nagoya University
- Hirohisa Watanabe🇯🇵Nagoya University
- Masahiko Yamamoto🇯🇵Aichi Gakuin University
- Gen Sobue🇯🇵 · autor de correspondenciaNagoya University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
The aim of this study was to explore the pathomechanism underlying the reduction of serum creatinine (Cr) concentrations in spinal and bulbar muscular atrophy (SBMA).
Methods
We evaluated blood chemistries, motor function, and muscle mass measured by dual-energy X-ray absorptiometry in male subjects with SBMA (n = 65), amyotrophic lateral sclerosis (ALS; n = 27), and healthy controls (n = 25). We also examined the intramuscular concentrations of creatine, a precursor of Cr, as well as the protein and mRNA expression levels of the creatine transporter (SLC6A8) in autopsy specimens derived from subjects who had SBMA and ALS and disease controls. Furthermore, we measured the mRNA expression levels of SLC6A8 in cultured muscle cells (C2C12) transfected with the polyglutamine-expanded androgen receptor (AR-97Q).
Results
Serum Cr concentrations were significantly lower in subjects with SBMA than in those with ALS (P < 0.001), despite similar muscle mass values. Intramuscular creatine concentrations were also lower in with the autopsied specimen of SBMA subjects than in those with ALS subjects (P = 0.018). Moreover, the protein and mRNA expression levels of muscle SLC6A8 were suppressed in subjects with SBMA. The mRNA levels of SLC6A8 were also suppressed in C2C12 cells bearing AR-97Q.
Interpretation
These results suggest that low serum Cr concentration in subjects with SBMA is caused by impaired muscle uptake of creatine in addition to being caused by neurogenic atrophy. Given that creatine serves as an energy source in skeletal muscle, increasing muscle creatine uptake is a possible therapeutic approach for treating SBMA.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC-ND).
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