Disease relevance of Slc12a1

• Cell proliferation under nonadhesive conditions was examined in anchorage-dependent mouse fibroblasts (3T3 and 3T6), in epithelial monkey kidney cells (BSC-1) and in four B16 melanoma cell variants that exhibit distinct metastatic properties [1].
• Chronic metabolic acidosis enhances the ability of the medullary thick ascending limb (MTAL) to absorb NH(4)(+) at least in part by stimulating the mRNA and protein expression of BSC1/NKCC2, the MTAL apical Na(+)-K(+)(NH(4)(+))-2Cl(-) co-transporter [2].

High impact information on Slc12a1

• Two Na-K-Cl cotransporters encoded by different genes have been identified in the mammalian kidney: BSC1/NKCC2 which localizes to the apical thick ascending limb of Henle and BSC2/NKCC1 which was isolated from a mouse IMCD cell line (mIMCD-3) but its localization has not been determined [3].
• TAL cells exhibited furosemide-sensitive Na-K((NH4)+)-Cl cotransport activity and endogenously expressed the 5.0-kilobase Nkcc2 transcript [4].
• Luciferase activity was 130-fold greater following transfection into TAL cells compared with transfection into cells that did not express Nkcc2 (NIH 3T3 fibroblasts) [4].
• The murine Nkcc2/Slcl2a1 gene encodes a bumetanide-sensitive Na-K-Cl cotransporter that is expressed exclusively in the kidney in the thick ascending limb of the loop of Henle [4].
• These results demonstrate that acid pH enhances the stability of BSC1 mRNA probably by activating pathways that act on the AU-rich 3'-UTR of BSC1 mRNA, which contributes to the renal response to metabolic acidosis [2].

Biological context of Slc12a1

• Localization of the renal Na-K-Cl cotransporter gene (Slc12a1) on mouse chromosome 2 [5].
• The C4 isoforms are generated by utilization of an alternative polyadenylation site located within the intron between exons 16 and 17 of the mBSC1 gene on chromosome 2; the resultant transcripts predict a truncated COOH terminus ending in a unique 55 amino acid sequence [6].
• We conclude that a PKC, likely of the novel type, nPKC, seems to be involved in PMA-induced reduction of expressed BSC1 and/or its ion transport function [7].

Anatomical context of Slc12a1

• The functional properties of alternatively spliced isoforms of the mouse apical Na+-K+-2Cl- cotransporter (mBSC1) were examined, using expression in Xenopus oocytes and measurement of 22Na+ or 86Rb+ uptake [8].
• Attempts to follow the expression of BSC1 in plasma membranes with either immunoblotting or radio-methionine pulse-chase were unsuccessful [7].
• A mouse monoclonal anti-alpha-tubulin antibody was used to investigate the disposition of the cytoskeletal microtubules of three tissue culture cell lines--J774 macrophages, BSC-1, and Vero cells--infected with the Brazil strain of Trypanosoma cruzi [9].

Associations of Slc12a1 with chemical compounds

• In addition to a urea metabolite (II) formed by transformation of the cyanamide functionality, another highly polar metabolite was found in mouse urine and in BSC-1, MDCK, and other cell culture incubations of [14C]LY217896 [10].
• Activating endogenous muscarinic receptors with 20 microM acetylcholine had no effect on expressed BSC1 fluxes [7].
• However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance [11].

References