A novel role for glucocorticoid-induced leucine zipper protein in epithelial sodium channel-mediated sodium transport. Export

@article{citeulike:494053, abstract = {The steroid hormone aldosterone stimulates sodium (Na+) transport in tight epithelia by altering the expression of target genes that regulate the activity and trafficking of the epithelial sodium channel (ENaC). We performed microarray analysis to identify aldosterone-regulated transcripts in mammalian kidney epithelial cells (mpkC-CD(c14)). One target, glucocorticoid-induced leucine zipper protein (GILZ), was previously identified by serial analysis of gene expression (SAGE); however, its function in epithelial ion transport was unknown. Here we show that GILZ expression is rapidly stimulated by aldosterone in mpkCCD(c14) and that GILZ, in turn, strongly stimulates ENaC-mediated Na+ transport by inhibiting extracellular signal-regulated kinase (ERK) signaling. In Xenopus oocytes with activated ERK, heterologous GILZ expression consistently inhibited phospho-ERK expression and markedly stimulated ENaC-mediated Na+ current, in a manner similar to that of U0126 (a pharmacologic inhibitor of ERK signaling). In mpkCCD(c14) cells, GILZ transfection similarly consistently inhibited phospho-ERK expression and stimulated transepithelial Na+ transport. Furthermore, aldosterone treatment of mpkCCD(c14) cells suppressed phospho-ERK levels with a time course that paralleled their increase of Na+ transport. Finally, GILZ expression markedly increased cell surface ENaC expression in epidermal growth factor-treated mammalian kidney epithelial cells, HEK 293. These observations suggest a novel link between GILZ and regulation of epithelial sodium transport through modulation of ERK signaling and could represent an important pathway for mediating aldosterone actions in health and disease.}, address = {Division of Nephrology, Department of Medicine, University of California at San Francisco, San Francisco, California 94143-0532, USA.}, author = {Soundararajan, R. and Zhang, T. T. and Wang, J. and Vandewalle, A. and Pearce, D.}, citeulike-article-id = {494053}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M508658200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16216878}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16216878}, day = {2}, doi = {10.1074/jbc.M508658200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {channel, enac, glucocorticoid}, month = {December}, number = {48}, pages = {39970--39981}, posted-at = {2006-02-06 00:41:52}, priority = {3}, title = {A novel role for glucocorticoid-induced leucine zipper protein in epithelial sodium channel-mediated sodium transport.}, url = {http://dx.doi.org/10.1074/jbc.M508658200}, volume = {280}, year = {2005} }

TY - JOUR ID - citeulike:494053 L3 - citeulike-article-id:494053 N2 - The steroid hormone aldosterone stimulates sodium (Na+) transport in tight epithelia by altering the expression of target genes that regulate the activity and trafficking of the epithelial sodium channel (ENaC). We performed microarray analysis to identify aldosterone-regulated transcripts in mammalian kidney epithelial cells (mpkC-CD(c14)). One target, glucocorticoid-induced leucine zipper protein (GILZ), was previously identified by serial analysis of gene expression (SAGE); however, its function in epithelial ion transport was unknown. Here we show that GILZ expression is rapidly stimulated by aldosterone in mpkCCD(c14) and that GILZ, in turn, strongly stimulates ENaC-mediated Na+ transport by inhibiting extracellular signal-regulated kinase (ERK) signaling. In Xenopus oocytes with activated ERK, heterologous GILZ expression consistently inhibited phospho-ERK expression and markedly stimulated ENaC-mediated Na+ current, in a manner similar to that of U0126 (a pharmacologic inhibitor of ERK signaling). In mpkCCD(c14) cells, GILZ transfection similarly consistently inhibited phospho-ERK expression and stimulated transepithelial Na+ transport. Furthermore, aldosterone treatment of mpkCCD(c14) cells suppressed phospho-ERK levels with a time course that paralleled their increase of Na+ transport. Finally, GILZ expression markedly increased cell surface ENaC expression in epidermal growth factor-treated mammalian kidney epithelial cells, HEK 293. These observations suggest a novel link between GILZ and regulation of epithelial sodium transport through modulation of ERK signaling and could represent an important pathway for mediating aldosterone actions in health and disease. IS - 48 JF - J Biol Chem SN - 0021-9258 AD - Division of Nephrology, Department of Medicine, University of California at San Francisco, San Francisco, California 94143-0532, USA. EP - 39981 TI - A novel role for glucocorticoid-induced leucine zipper protein in epithelial sodium channel-mediated sodium transport. VL - 280 SP - 39970 KW - channel KW - enac KW - glucocorticoid AU - Soundararajan, R AU - Zhang, TT AU - Wang, J AU - Vandewalle, A AU - Pearce, D PY - 2005/12/02/ UR - http://dx.doi.org/10.1074/jbc.M508658200 ER -