[Space flight/bedrest immobilization and bone. Development of inhibitors for atrophy caused by unloading stress].

Abstract

Muscle atrophy caused by unloading stress is a serious problem in bed rest patients or astronauts. In our previous studies, we revealed that induction and activation of ubiquitin ligase Cbl-b played an important role in skeletal muscle atrophy caused by unloading stress. Under muscle atrophy conditions, Cbl-b interacted with and degraded IRS-1 (insulin receptor substrate 1) that is a central molecule in the IGF-1 signaling pathway. In addition, we developed a Cbl-b inhibitor (Cblin) that a pentapeptide mimetic of tyrosin608-phosphorylated IRS-1, DGpYMP. This Cblin peptide inhibited Cbl-b mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of MAFbx/atrogin-1. We are further developing Cbl-b inhibitors that are more effective than an original Cblin peptide.

• Authors: Shigetada Kondo, Ochi Arisa, Shohei Kohno, Tomoki Abe, Kenro Utsunomiya, Hikaru Nagano, Takuro Suto, Chisato Tomida, Naoko Yamagishi, Katsuya Hirasaka, Ayako Maita, Yushi Okumura, Takeshi Nikawa
• Journal: Clinical calcium (Clin Calcium) Vol. 22 Issue 12 Pg. 1879-85 (Dec 2012) ISSN: 0917-5857 [Print] Japan
• PMID: 23187081 (Publication Type: English Abstract, Journal Article, Review)

Topics

• Bed Rest
• Bone and Bones (metabolism)
• Humans
• Muscular Atrophy (drug therapy, etiology, prevention & control)
• Space Flight
• Stress, Mechanical
• Stress, Physiological