Several lines of evidence in diverse cell types point to
the involvement of Egr transcription factors in the
response to mechanical stress. Egr expression induced
by 3-D-clinorotation occurs within 90 minutes of
stimulation, indicating that the Egr genes are in close
temporal proximity to the mechanical stress
“receptor.” Consistent with the role of oxidants as the
second messengers of Egr activation and downstream
unloading responses, the ERK1/2 pathway, a common
target of oxidative signaling, was activated by 3-D-
clinorotation and H 2 O 2. Together, these results are
consistent with the findings of other laboratories; they
showed that immobilization or tail suspension
increased oxidative stress-dependent signaling in rat
skeletal muscles. Recent studies have identified
several signaling molecules, such as ASK1, that
mediate oxidative stress-dependent activation of
MAPK signaling. An important area for further
investigation will be to identify the molecules that
regulate ROS production in distinct cellular
compartments (plasma membrane, mitochondria) in
response to unloading. It is anticipated that these
molecules may be the direct receptors/sensors for
unloading stress. This hypothesis is supported by
previous finding that the disrupted expression of
cytoskeletal genes, especially mitochondria-anchoring
protein genes, is associated with large imbalances in
the expression of genes encoding diverse members of
the electron transport system in the mitochondria of
space-flown skeletal muscle.
PUBLICATION(S)
Abe T, Hirasaka K, Kagawa S, et al. Cbl-b is a critical regulator of macrophage activation
associated with obesity-induced insulin resistance in mice. Diabetes. January 24,
2013;62(6):1957-1969. doi: 10.2337/db12-0677.
Abe T, Kohno S, Yama T, et al. Soy glycinin contains a functional inhibitory sequence against
muscle-atrophy-associated ubiquitin ligase Cbl-b. International Journal of Endocrinology.
2013;2013(907565):1-11. doi: 10.1155/2013/907565.
Teshima-Kondo S, Ochi A, Kohno S, et al. Spaceflight/bedrest immobilization and bone
development of inhibitors for atrophy caused by unloading stress. Clinical Calcium. December
2012;22(12):1879-1885. doi: CliCa121218791885.
ISS023E025830-Expedition 23 flight
engineer and Japan Aerospace Exploration
Agency (JAXA) astronaut Soichi Noguchi is
photographed with hardware for the
Molecular Mechanism of Microgravity-
Induced Skeletal Muscle Atrophy (MyoLab)
experiment in the Kibo Japanese Experiment
Pressurized Module (JPM). JAXA image.