Ayako Ohno

Skeletal muscle atrophy caused by unloading is characterized by both decreased responsiveness to myogenic growth factors (e.g., insulin-like growth factor 1 [IGF-1] and insulin) and increased proteolysis. Here, we show that unloading stress resulted in skeletal muscle atrophy through the induction and activation of the ubiquitin ligase Cbl-b. Upon induction, Cbl-b interacted with and degraded the IGF-1 signaling intermediate IRS-1. In turn, the loss of IRS-1 activated the FOXO3-dependent induction of atrogin-1/MAFbx, a dominant mediator of proteolysis in atrophic muscle. Cbl-b-deficient mice were resistant to unloading-induced atrophy and the loss of muscle function. Furthermore, a pentapeptide mimetic of tyrosine(608)-phosphorylated IRS-1 inhibited Cbl-b-mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of atrogin-1/MAFbx. Our results indicate that the Cbl-b-dependent destruction of IRS-1 is a critical dual mediator of both increased protein degradation and reduced protein synthesis observed in unloading-induced muscle atrophy. The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy.

The feeding habits of 3 dominant myctophid fishes, Diaphus theta (vertical migrant), Stenobrachius leucopsarus (semi-migrant), and S. nannochir (non-migrant), were studied in relation to their diel vertical migration patterns using time-series sampling during the summers of 1994 to 1996 in the subarctic and transitional waters of the western North Pacific. D. theta and S. leucopsarus fed mainly on euphausiids (mainly Euphausia pacifica), copepods (mainly Metridia pacifica and the Neocalanus plumchrus/flemingeri group), and amphipods (mainly the Themisto japonica /pacifica group). The prey of S. nannochir was mainly copepods, but the species were different from those preyed on by D. theta and S. leucopsarus. D. theta fed on euphausiids, with 1 feeding peak during the daytime and another at night, but fed on amphipods only at night and on copepods throughout the entire diel cycle. The vertical migratory component of S. leucopsarus showed a significant diel feeding periodicity, feeding on euphausiids, copepods, and amphipods from dusk to midnight, while the non-migratory component did not feed actively at nighttime, and had a high frequency of empty stomachs. The non-migratory S. nannochir showed no diel feeding periodicity. The average ratio of stomach content weight/body weight was 2.2% during the day and 2.0% at night in D. theta, 0.8% during the daytime and 1.1% at night in the migratory S. leucopsarus, 0.6% at night in the nonmigratory S. leucopsarus, and 0.07 to 0.13% (avg. 0.11%) in S. nannochir.