Aldosterone induction and epithelial distribution of CHIF

Abstract

CHIF is a recently cloned, corticosteroid-induced gene which evokes K+ channel activity in oocytes (B. Attali, H. Latter, N. Rachamim, and H. Garty. Proc. Natl. Acad. Sci. USA 92: 6092-6096, 1995). To further characterize the possible role of this gene in epithelial ion transport, we have studied its epithelial distribution and hormonal induction. Northern hybridizations indicate that the zonal distribution of CHIF mRNA in kidney is: papilla >>medulla>> cortex. High levels of CHIF were also detected in a primary culture from inner medullary collecting duct (IMCD). Perfusing rats with < 20 nM aldosterone through osmotic minipumps evoked a 22.4 +/- 1.9-fold increase in colonic CHIF. A significant increase was observed 3 h after administrating the corticosteroid, but maximal response was detected only after a 72-h incubation. This response appears to be mineralocorticoid specific; perfusing or injecting rats with maximal doses of dexamethasone did not evoke a further increase in CHIF mRNA. In contrast, high levels of CHIF are expressed in kidney papilla and IMCD primary culture, irrespective of corticosteroid treatment. Thus, like the apical Na+ channel and the H(+)-K(+)-adenosinetriphosphatase, CHIF is mineralocorticoid induced in the colon but constitutively expressed in kidney.

Effects of water restriction on gene expression in mouse renal medulla: identification of 3βHSD4 as a collecting duct protein

“…4 was not significantly altered (108 Ϯ 9 compared with 100 Ϯ 10% in control IM). CHIF mRNA and protein have previously been reported as responding differently; CHIF mRNA and protein is elevated by aldosterone in the colon (1, 27); however, in the kidney CD CHIF protein increases with aldosterone, but CHIF mRNA does not (30,31). The mRNA for the ␣-subunit of Na-KATPase was significantly increased in abundance (1.53 Ϯ 0.2 compared with control 1.00 Ϯ 0.14, P Ͻ 0.05) as was the mRNA for the ␤-subunit of Na-K-ATPase (2.43 Ϯ 0.13 compared with control 1.00 Ϯ 0.44, P Ͻ 0.05).…”

Structural Interactions between FXYD Proteins and Na+,K+-ATPase

“…Dibromobimane-induced Cross-linking of CHIF to the ␣ Subunit in Native Colonocyte Membranes-Rat colonic membranes express high levels of CHIF mRNA and protein especially after feeding the rats high K ϩ or low Na ϩ diets (31,38,39). Membranes obtained from such colonocytes are suitable for demonstrating ␣-CHIF cross-links.…”

New ideas about aldosterone signaling in epithelia

“…The finding that MR and GR have distinct effects on cognition and learning mediated by the hippocampus supports the possibility of unique MR and GR cis-acting elements or that unique protein-protein interactions involving these distinct receptors convey different signals (43, 44). MR and GR also have distinguishable actions in the colon (9,27,39,181). Further support for unique cis-acting elements comes from the study of model systems.…”

“…CHIF was first identified as a corticosteroid-induced gene in rat colon (6). CHIF is expressed in epithelia of the distal colon and nephron (6,33,181). This protein is localized primarily to the basolateral membrane, where it presumably interacts with its final effector to stimulate transport (150).…”

“…This protein is localized primarily to the basolateral membrane, where it presumably interacts with its final effector to stimulate transport (150). Corticosteroids via MR but not GR regulate CHIF expression at the level of transcription in colon but not kidney (27,33,181,182). Induction of CHIF in the colon in response to corticosteroids is a primary action independent of de novo protein synthesis, with CHIF levels increasing as early as 1 h after steroid treatment (27).…”