Space shuttle flight (STS‐90) enhances degradation of rat myosin heavy chain in association with activation of ubiquitin‐proteasome pathway

Abstract

To elucidate the mechanisms of microgravity‐induced muscle atrophy, we focused on fast‐type myosin heavy chain (MHC) degradation and expression of proteases in atrophied gastrocnemius muscles of neonatal rats exposed to 16‐d spaceflight (STS‐90). The spaceflight stimulated ubiquitination of proteins, including a MHC molecule, and accumulation of MHC degradation fragments in the muscles. Semiquantitative reverse transcriptase‐polymerase chain reaction revealed that the spaceflight significantly increased mRNA levels of cathepsin L, proteasome components (RC2 and RC9), polyubiquitin, and ubiquitin‐conjugating enzyme in the muscles, compared with those of ground control rats. The levels of μ‐calpain, m‐calpain, cathepsin B, and cathepsin H mRNAs were not changed by the spaceflight. We also found that tail‐suspension of rats for 10 d or longer caused the ubiquitination and degradation of MHC in gastrocnemius muscle, as was observed in the spaceflight rats. In the muscle of suspended rats, these changes were closely associated with activation of proteasome and up‐regulation of expression of mRNA for the proteasome components and polyubiquitin. Administration of a cysteine protease inhibitor, E‐64, to the suspended rats did not prevent the MHC degradation. Our results suggest that spaceflight induces the degradation of muscle contractile proteins, including MHC, possibly through a ubiquitin‐dependent proteolytic pathway.

Spaceflight results in increase of thick filament but not thin filament proteins in the paramyosin mutant of Caenorhabditis elegans

“…It is reported that the ubiquitin-dependent proteolytic pathway causes the microgravity induced muscular atrophy, and micro-array data indicates the up-regulation of the expression of ubiquitin ligases in the space-flown rat (Ikemoto et al, 2001;Nikawa et al, 2004). In our data, body-wall muscle of unc-15(e73) animal occurred atrophy after spaceflight (Fig.…”

Determinants of Disuse-Induced Skeletal Muscle Atrophy: Exercise and Nutrition Countermeasures to Prevent Protein Loss

“…Recent investigations have indicated that the three primary proteolytic systems may work as partners during muscle proteolysis (17,55). The ubiquitin-proteasome pathway appears responsible for degradation of the bulk of proteins, mainly myofibrillar proteins, in conditions of decreased muscle use (55,88,89). However, there is an extensive consensus that intact myofibrillar proteins cannot be degraded by the proteasome (90); consequently, the initial cleavage of myofibrillar proteins requires other proteases (87).…”

Oxidative and proteolytic profiles of the right and left heart in a model of cancer-induced cardiac cachexia

“…In recent years, free radicals have been implicated as important modulators of biological processes, particularly with respect to processes involved in the regulation of skeletal and cardiac muscle mass [5][6][7][8]. Oxidative stress is characterized by an imbalance between the production of reactive oxygen/nitrogen species and their neutralization through antioxidant defence systems [9].…”