title: [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.affiliation: Department of Nutrition and Physiology, Institute of Health Biosciences, University of Tokushima, Japan.
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kondo
authors.forename: Ochi
authors.initials: O
authors.lastname: Arisa
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.forename: Kenro
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nagano
authors.forename: Takuro
authors.initials: T
authors.lastname: Suto
authors.forename: Chisato
authors.initials: C
authors.lastname: Tomida
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamagishi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.forename: Ayako
authors.initials: A
authors.lastname: Maita
authors.forename: Yushi
authors.initials: Y
authors.lastname: Okumura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
mesh_terms: D001510:Bed Rest; D001842:Bone and Bones / Q000378:metabolism*; D006801:Humans; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D013026:Space Flight; D013314:Stress, Mechanical; D013312:Stress, Physiological