Changes in gene expression and signal transduction in microgravity.
Studies from space flights over the past three decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. This laboratory has recently studied gene growth and activation of normal osteoblasts (MC3T3-El) during spaceflight. Osteoblast cells were grown on glass coverslips and loaded in the Biorack plunger boxes. The osteoblasts were launched in a serum deprived state, activated in microgravity and collected in microgravity. The osteoblasts were examined for changes in gene expression and signal transduction. Approximately one day after growth activation significant changes were observed in gene expression in 0-G flight samples. Immediate early growth genes/growth factors cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA showed a significant diminished mRNA induction in microgravity FCS activated cells when compared to ground and 1-G flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of reference gene mRNA between the ground, 0-G and 1-G samples. The data suggest that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-G. Here we examine ground-based and space flown data to help us understand the mechanism of bone loss in microgravity.
Hughes-Fulford
M
M
Lab of Cell Growth, Department of Veteran's Affairs Medical Center and University of California San Fransico, CA 94121, USA. milliehf@aol.com
D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology*; D016762:Genes, fos; D006801:Humans; D018471:Hypergravity; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013026:Space Flight; D014893:Weightlessness
D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone