ID 110024
Title Transcription
ハイヨウセイ キン イシュク オ フセグ コウユビキチンカ ペプチド Cblin Cbl-b inhibitor ノ コウキノウカ
Title Alternative
Development of anti-ubiquitination oligopeptide, Cblin : Cbl-b inhibitor that prevents unloading-induced skeletal muscle atrophy
Author
Ochi, Arisa Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima
Kitahata, Kanako Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima
Hirasaka, Katsuya Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima KAKEN Search Researchers
Maita-Ohno, Ayako Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima
Teshima-Kondo, Shigetada Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima KAKEN Search Researchers
Okumura, Yuushi Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima KAKEN Search Researchers
Nagano, Keisuke First Institute of New Drug Discovery, Otsuka Pharmaceutical Co.
Kawamura, Tomoyuki Departments of Pharmaceutical Chemistry Institute of Health Biosciences, University of Tokushima
Nemoto, Hisao Departments of Pharmaceutical Chemistry Institute of Health Biosciences, University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Nikawa, Takeshi Departments of Nutritional Physiology Institute of Health Biosciences, University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
skeletal muscle atrophy
dexamethasone
Cbl-b
IRS-1
N-terminus myristoylation
Content Type
Journal Article
Description
Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors and increased proteolysis. In our previous studies, it has been shown that ubiquitin ligase Cbl-b interacted and degraded the IGF-1 signaling intermediate IRS-1. We also reported that a peptide mimetic of tyrosin608-phosphorylated IRS-1 (DGpYMP), named Cblin, Cbl-b inhibitor. However, Cblin may tend to be degraded by aminopeptidase in vivo. We aimed to confirm whether Cblin inhibiter muscle atrophy caused by glucocorticoids in mouse C2C12 myotubes, and effects of the modified Cblin N-terminus to prevent it from degradation. Pretreatment with Cblin significantly prevented the decrease in diameters of C2C12 myotubes treated with dexamethasone, and IRS-1 degradation, expression of atrogenes mRNA was repressed, and phosphorylation of Akt/mTOR was also protected. Moreover, the 50% inhibitory concentration of N -myristoylated Cblin and Cblin for Cbl-b-mediated IRS-1 ubiquitination was 35μM and 120μM, respectively. In addition, N -myristoylated Cblin significantly inhibited the dexamethasone-induced reduction of myotube diameter. Taken together, these results suggest that Cblin Cblin prevented the dexamethasone induced myotube atrophy, and N -myristoyled Cblin is more effective than nonmodified Cblin in prevention of muscle atrophy.
Journal Title
四国医学雑誌
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
68
Issue
5-6
Start Page
217
End Page
222
Sort Key
217
Published Date
2012-12-25
FullText File
language
jpn
TextVersion
Publisher
departments
Pharmaceutical Sciences
Medical Sciences