Altered Expression Of Target Genes Research Articles

Corticosterone increases serotonin type-3 receptor mRNA in rat pheochromocytoma-12 cells

Serotonin type-3 (5-HT3) receptors are cation permeable membrane receptors which are involved in modulation of calcium entry in neuronal cells. Along with other ion-channels such as the N-methyl- d-aspartate receptor, it appears to be a target for the actions of ethanol and has been the focus of considerable work in this regard. Since in animals, ethanol exposure results in elevations of corticosteroids in both acute and chronic conditions, we studied the effects of both ethanol and corticosteroid exposure on 5-HT3 gene expression in an in situ pheochromocytoma-12 (PC12) cell model. We found that ethanol exposure alone (80 mM×4 days) did not significantly alter target gene expression. Corticosterone (CORT) (50, 150, and 300 ng/ml) resulted in significant increases in 5-HT3 expression which were attenuated by mifeprestone (50 ng/ml). Ethanol in combination with CORT did not significantly alter the increase in 5- HT3 mRNA seen with CORT alone. We conclude that in PC12 cells, exposure to CORT at physiologically relevant concentrations increases 5-HT3 gene expression.

β‐Adrenergic treatment of C6 glioma cells produces opposite changes in c‐fos and c‐jun mRNA levels

The AP1 transcriptional complex is a heterodimer composed of proteins encoded by the fos and jun proto-oncogene families. Changes in the concentration and composition of AP1 occur after cells are perturbed in a variety of different ways (Curran, in Reddy et al., eds. "The Oncogene Handbook," Amsterdam: Elsevier, pp 307-325, 1988; Sonnenberg et al., Neuron 3:359-365, 1989). Transient changes in AP1 content presumably result in altered expression of AP1-regulated target genes, that help to mediate the cell's long-term response to changes in its environment. One factor that may be important in determining which target genes are regulated by AP1 in a given context is the identity of the jun family member present in the complex (Chiu et al., Cell 59:979-986, 1989; Schutte et al., Cell 59:987-997, 1989). Fos induction has been demonstrated after binding of beta-adrenergic ligands to their cell surface receptors (Barka et al., Mol Cell Biol 6:2984-2989, 1986; Gubits et al., Mol Brain Res 6: 39-45, 1989; Arenander et al., J Neurosci Res 24: 107-114, 1989; Mocchetti et al., Proc Natl Acad Sci USA 86:3891-3895, 1989). However, the response of the jun gene family to this treatment has not been reported. We have therefore examined the effect of beta-adrenergic receptor activation on the expression of c-fos, c-jun, and junB mRNA levels in C6 glioma cells. Our results indicate that c-fos and junB mRNA levels are increased by 52- and 2.7-fold, respectively, after 45 min of isoproterenol (IPR) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)