SGK1 Regulation of Epithelial Sodium Transport

Pearce, David

doi:10.1159/000070245

Cited by 147 publications

(141 citation statements)

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“…In this fish, OSTF1 mRNA and protein levels rapidly increased in response to hyperosmotic stress. This finding is reminiscent of SGK1, which is also regulated by both aldosterone and osmotic stress in kidney collecting duct cells (38) and other cell types as well (39,40). The rapid activation kinetics is again characteristic of immediate early genes like SGK1.…”

Section: Discussionmentioning

confidence: 83%

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Soundararajan

Wang

Melters

et al. 2007

Journal of Biological Chemistry

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Glucocorticoid-induced leucine zipper protein (GILZ) is expressed in both epithelial and immune tissues and modulates a variety of cellular functions, including proliferation and epithelial sodium channel (ENaC) activity. A number of reports have described various GILZ activities, focusing on a single isoform with molecular mass of ϳ17 kDa, now termed GILZ1. In GILZ immunoblots using a newly developed antiserum, we detected multiple species in extracts from cultured kidney cells. Mass spectrometric analysis revealed that one of these represented a previously uncharacterized distinct isoform of GILZ, GILZ2. Rapid amplification of cDNA ends was used to clone cDNAs corresponding to four isoforms, which, in addition to GILZ1 and GILZ2, included new isoforms GILZ3 and GILZ4. Heterologous expression of these four GILZ isoforms in cultured cells revealed striking functional differences. Notably, GILZ1 was the only isoform that significantly stimulated ENaCmediated Na ؉ current in a kidney collecting duct cell line, although GILZ2 and GILZ3 also stimulated ENaC surface expression in HEK 293 cells. GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation. Interestingly, GILZ4, which had no effect on either ENaC or ERK, potently suppressed cellular proliferation, as did GILZ1, but not GILZ2 or GILZ3. Finally, rat and mouse tissues all expressed multiple GILZ species but varied in the relative abundance of each. These data suggest that multiple GILZ isoforms are expressed in most cells and tissues and that these play distinct roles in regulating key cellular functions, including proliferation and ion transport. Furthermore, GILZ inhibition of ERK appears to play an essential role in stimulation of cell surface ENaC but not in inhibition of proliferation. Glucocorticoid-induced leucine zipper (GILZ)3 is a small leucine zipper protein of ϳ17 kDa. As its name implies, GILZ was first discovered as a dexamethasone-induced transcript in murine thymocytes, which it protects from apoptosis induced by treatment with anti-CD3 antibody (1). It is a member of the TSC22D (transforming growth factor ␤1-stimulated clone 22 domain) family of proteins that are widely expressed and appear to impact multiple biological processes (2-5). TSC22D1 (or, simply, TSC22) was first isolated based on its rapid and transient transcriptional induction by transforming growth factor ␤1 (6). It is a potential tumor suppressor gene and has been shown to down-regulate cell proliferation and induce apoptosis in human salivary gland (7,8). Its expression in human fetal tissues (9) and, more recently, its detection at sites of epithelial-mesenchymal interactions during mouse embryogenesis (10) suggest an important role for this protein during vertebrate development. A similar role has been identified for the TSC22 homologue, bunched, in developing Drosophila larvae (11). TSC22D2 and TSC22D4 are expressed in renal cortex, medulla, and papilla and are involved in adaptation of these cells to hypertonicity (4). These two transcripts are signifi...

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Section: Discussionmentioning

confidence: 83%

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Soundararajan

Wang

Melters

et al. 2007

Journal of Biological Chemistry

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“…Sgk1 is a known target involved in various forms of cell stress and regulates several fundamental processes including ion channel function and neuronal excitability (Lang and Shumilina, 2013;Pearce, 2003). Sgk1 has also been proposed to play a critical role in memory performance, as fast learning rats have higher levels of Sgk1 mRNA than slow learners, and Sgk1 inhibition impairs, while Sgk1 overexpression enhances memory consolidation (Lee et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Hippocampal gene expression induced by cold swim stress depends on sex and handling

Bohacek

Manuella

Roszkowski

et al. 2015

Psychoneuroendocrinology

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Summary: Stress-related disorders such as PTSD and depression are more prevalent in women than men. One reason for such discordance may be that brain regions involved in stress responses are more sensitive to stress in females. Here, we compared the effects of acute stress on gene transcription in the hippocampus of female and male mice, and also examined the involvement of two key stress-related hormones, corticosterone and corticotropin releasing hormone (Crh). Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), we measured gene expression of Fos, Per1 and Sgk1 45 min after exposure to brief cold swim stress. Stress induced a stronger increase in Fos and Per1 expression in females than males. The handling control procedure increased Fos in both sexes, but occluded the effects of stress in males. Further, handling increased Per1 only in males. Sgk1 was insensitive to handling, and increased in response to stress similarly in males and females. The transcriptional changes observed after swim stress were not mimicked by corticosterone injections, and the stress-induced increase in Fos, Per1 and Sgk1 could neither be prevented by pharmacologically blocking glucocorticoid receptor (GR) nor by blocking Crh receptor 1 (Crhr1) before stress exposure. Finally, we demonstrate that the effects are stressor-specific, as the expression of target genes could not be increased by brief restraint stress in either sex. In summary, we find strong effects of acute swim stress on hippocampal gene expression, complex interactions between handling and sex, and a remarkably unique response pattern for each gene. Overall, females respond to a cold swim challenge with stronger hippocampal gene transcription than males, independent of two classic mediators of the stress response, corticosterone and Crh. These findings may have important implications for understanding the higher vulnerability of women to certain stress-related neuropsychiatric diseases. In summary, we find strong effects of acute swim stress on hippocampal gene expression, complex interactions between handling and sex, and a remarkably unique response pattern for each gene. Overall, females respond to a cold swim challenge with stronger hippocampal gene transcription than males, independent of two classic mediators of the stress response, corticosterone and Crh. These findings may have important implications for understanding the higher vulnerability of women to certain stress-related neuropsychiatric diseases.

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“…14 AVP also induces cAMP-mediated translocation of ENaC to the luminal membrane. 15 Furthermore, ENaC is regulated by Nedd4 -2 and SGK1 16 and several other factors. 17 The NHE3 is regulated by the Na ϩ /H ϩ exchanger regulatory factor (NHERF2), scaffolding various proteins close to NHE3.…”

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confidence: 99%

Acute Rejection Modulates Gene Expression in the Collecting Duct

Edemir

Reuter²,

Borgulya³

et al. 2008

Journal of the American Society of Nephrology

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Kidney transplantation, especially when associated with acute rejection, leads to changes in the expression of many genes, including those encoding solute transporters and water channels. In a rat model of acute rejection after allogeneic renal transplantation, impaired renal function, increased urine volume, and increased fractional excretion of sodium were observed. Gene array analysis revealed that these findings were associated with significant downregulation of water channels (aquaporin-1, -2, -3, and -4) and transporters of sodium, glucose, urea, and other solutes. In addition, changes in expression of various receptors, kinases, and phosphatases that modulate the expression or activity of renal transport systems were observed. Syngeneic transplantation or treatment with cyclosporine A following allogeneic transplantation did not impair graft function but did lead to the downregulation of aquaporin-1, -3, and -4 and several solute transporters. However, expression of aquaporin-2 and the epithelial sodium channel did not change, suggesting that the downregulation of these transporters following allogeneic transplantation is rejection-dependent. In conclusion, changes in gene expression may explain the impaired handling of solute and water after allogeneic transplantation, especially during acute rejection. Treatment with cyclosporine A improves the regulation of solute and water by preventing the downregulation of aquaporin-2 and epithelial sodium channel, even though many other transporter genes remain downregulated. Renal transplantation (TX) in humans is often accompanied by increased transport capacities of the graft and disturbances in salt and water homeostasis. 1-3 Half-life of grafts with normal function after TX is 11.5 yr compared with 7.2 yr for those with impaired renal function. 4 A better understanding of the underlying cellular and molecular mechanisms leading to such changes may help to increase longterm graft survival.Previously, using an allogeneic rat renal TX (aTX) model, we have demonstrated acute changes in expression and function of several transporters and receptors after aTX. 5,6 For example, the expression of Na ϩ /H ϩ -exchanger-3 (NHE3), aquaporin-2 (AQP2), and the epithelial Na ϩ channel (ENaC) were downregulated at the protein and mRNA level. Major transporters for water and Na ϩ reabsorption in the collecting duct (CD) are ENaC and AQP2. 7 The expression and activity of AQP2 are regulated by the antidiuretic hormone (vasopressin, AVP) via the G-protein coupled AVP-2 receptor (V2R). 8 The binding of AVP to the V2R leads to the activation of the G-protein Gs, followed by activation of adenylate cyclase (AC), increased cyclic adenosine monophosphate (cAMP) levels, activation of protein kinase A (PKA), and finally phosphorylation of AQP2 9 and translocation to the

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SGK1 Regulation of Epithelial Sodium Transport

Cited by 147 publications

References 57 publications

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Hippocampal gene expression induced by cold swim stress depends on sex and handling

Acute Rejection Modulates Gene Expression in the Collecting Duct

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