Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 33
Small GTPase Ras and Rho expression in rat osteoblasts during spaceflight
Yasuhiro Kumei 1 , Sadao Morita 1 , Hitoyata Shimokawa 1 , Kei-ichi Ohya 1 ,
Hisako Katano 2 , Hideo Akiyama 3 , Masahiko Hirano 3
1 Tokyo Medical and Dental University, Tokyo, Japan
2 University of Tokyo Medical Science Institute, Tokyo, Japan
3 Toray Research Center, Kamakura, Japan
Rat osteoblasts were cultured for 4 and 5 days aboard Space Shuttle and solubilized after a 24
hr-treatment with 1",25 dihydroxyvitamin D3. The mRNA levels of Ras and Rho were
analyzed by quantitative RT-PCR normalized to glyceraldehyde 3-phosphate dehydrogenase.
The small GTPase Ras and Rho are activated by GEF (guanine nucleotide exchange factor)
and deactivated by GAP (GTPase-activating factor). Recently we reported that expression of
Ras GEF, Ras-GRF (guanine nucleotide releasing factor) increased to 2- to 5-fold of the
ground controls, during spaceflight. Ras-GRF acts downstream G-protein coupled receptors,
whereas another Ras GEF, SOS (son of sevenless) activates Ras after binding to adaptor
protein Grb2 of receptor tyrosine kinase. The SOS mRNA levels also increased to 3- to 5-fold
during spaceflight, although Ras GAP expression was not altered. Ras activation was
followed by MAP kinase cascades including ERK1/2 expression, and FAK (focal adhesion
kinase) increased during spaceflight. Cdc42 is a Rho family protein that responds to
environmental stress and induces JNK (Jun-N-terminal kinase). Both Cdc42 GAP and GEF
expression was increased 2-fold in the flight cultures, as compared to the ground controls.
Accelerated Cdc42 turnover might result in 2-fold increase of JNK expression. Rho plays
important roles in actin rearrangement. Microgravity may alter physiological change of rat
osteoblasts at least partly via small GTPase.
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