| First Author | Battula S | Year | 2011 |
| Journal | Am J Physiol Renal Physiol | Volume | 301 |
| Issue | 1 | Pages | F94-100 |
| PubMed ID | 21511694 | Mgi Jnum | J:174108 |
| Mgi Id | MGI:5051894 | Doi | 10.1152/ajprenal.00650.2010 |
| Citation | Battula S, et al. (2011) Tumor necrosis factor-{alpha} is an endogenous inhibitor of Na+-K+-2Cl- cotransporter (NKCC2) isoform A in the thick ascending limb. Am J Physiol Renal Physiol 301(1):F94-F100 |
| abstractText | The effects of TNF gene deletion on renal Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) expression and activity were determined. Outer medulla from TNF(-/-) mice exhibited a twofold increase in total NKCC2 protein expression compared with wild-type (WT) mice. This increase was not observed in TNF(-/-) mice treated with recombinant human TNF (hTNF) for 7 days. Administration of hTNF had no effect on total NKCC2 expression in WT mice. A fourfold increase in NKCC2A mRNA accumulation was observed in outer medulla from TNF(-/-) compared with WT mice; NKCC2F and NKCC2B mRNA accumulation was similar between genotypes. The increase in NKCC2A mRNA accumulation was attenuated when TNF(-/-) mice were treated with hTNF. Bumetanide-sensitive O(2) consumption, an in vitro correlate of NKCC2 activity, was 2.8 +/- 0.2 nmol.min(-1).mg(-1) in medullary thick ascending limb tubules from WT, representing approximately 40% of total O(2) consumption, whereas, in medullary thick ascending limb tubules from TNF(-/-) mice, it was 5.6 +/- 0.3 nmol.min(-1).mg(-1), representing approximately 60% of total O(2) consumption. Administration of hTNF to TNF(-/-) mice restored the bumetanide-sensitive component to approximately 30% of total O(2) consumption. Ambient urine osmolality was higher in TNF(-/-) compared with WT mice (2,072 +/- 104 vs. 1,696 +/- 153 mosmol/kgH(2)O, P < 0.05). The diluting ability of the kidney, assessed by measuring urine osmolality before and after 1 h of water loading also was greater in TNF(-/-) compared with WT mice (174 +/- 38 and 465 +/- 81 mosmol/kgH(2)O, respectively, P < 0.01). Collectively, these findings suggest that TNF plays a role as an endogenous inhibitor of NKCC2 expression and function. |
