title: Effect of simulated microgravity on oxidation-sensitive gene expression in PC12 cells.
abstract: Oxygen utilization by and oxygen dependence of cellular processes may be different in biological systems that are exposed to microgravity (micro-g). A baseline in which cellular changes in oxygen sensitive molecular processes occur during micro-g conditions would be important to pursue this question. The objective of this research is to analyze oxidation-sensitive gene expression in a model cell line [rat pheochromocytoma (PC12)] under simulated micro-g conditions. The PC12 cell line is well characterized in its response to oxygen, and is widely recognized as a sensitive model for studying the responses of oxygen-sensitive molecular and cellular processes. This study uses the rotating wall vessel bioreactor (RWV) designed at NASA to simulate micro-g. Gene expression in PC12 cells in response to micro-g was analyzed by DNA microarray technology. The microarray analysis of PC12 cells cultured for 4 days under simulated micro-g under standardized oxygen environment conditions revealed more than 100 genes whose expression levels were changed at least twofold (up-regulation of 65 genes and down-regulation of 39 genes) compared with those from cells in the unit gravity (unit-g) control. This study observed that genes involved in the oxidoreductase activity category were most significantly differentially expressed under micro-g conditions. Also, known oxidation-sensitive transcription factors such as hypoxia-inducible factor-2alpha, c-myc, and the peroxisome proliferator-activated receptor-gamma were changed significantly. Our initial results from the gene expression microarray studies may provide a context in which to evaluate the effect of varying oxygen environments on the background of differential gene regulation of biological processes under variable gravity conditions.
authors.affiliation: Department of Mechanical Engineering, University of Cincinnati, Cincinnati, OH 45221, USA.
authors.forename: Ohwon
authors.initials: O
authors.lastname: Kwon
authors.forename: Maureen
authors.initials: M
authors.lastname: Sartor
authors.forename: Craig R
authors.initials: CR
authors.lastname: Tomlinson
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Millard
authors.forename: Mark E
authors.initials: ME
authors.lastname: Olah
authors.forename: John M
authors.initials: JM
authors.lastname: Sankovic
authors.forename: Rupak K
authors.initials: RK
authors.lastname: Banerjee