Tissue-specific modulation of Na, K-ATPase α-subunit gene expression in uremic rats

Abstract

Chronic renal failure in the rat is associated with an impaired extrarenal potassium handling, whereas a renal adaptive mechanism of the remaining nephrons has been described. To understand the molecular basis of potassium homeostasis during renal failure we investigated the in vitro pump activity and the catalytic mRNA transcription in three different tissues: skeletal muscle, isolated adipocytes and kidney. The activity of the sodium pump, as measured by ouabain-sensitive 86Rb/K uptake in isolated adipocytes and skeletal muscle fibers, revealed a significant reduction of the pump activity in uremic rats. The reduction of the Na, K-ATPase activity in adipose tissue was associated with a similar decrement of both catalytic subunits (alpha 1 and alpha 2), whereas in the skeletal muscle tissue was only related to a decrease in the activity of the alpha 1 isoform. The expression of rat Na, K-ATPase catalytic isoforms mRNAs in kidney, muscle and adipose tissue from control and chronic renal failure rats was investigated at the molecular level with cDNA probes specific for the catalytic isoforms (alpha 1 and alpha 2). Northern blot analysis revealed that the respective catalytic mRNAs of uremic rats are regulated in a tissue-specific manner that are in agreement with the sodium-potassium pump activity. Muscle and adipose tissue showed a decrement in the levels of expression for the alpha 1 isoform mRNA. In contrast to these tissues, an increment in alpha 1 mRNA expression was observed in the kidney of rats with chronic renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension inBr/+ adult mice

“…Therefore, the physiological defects in fluid reabsorption seen in Br/ϩ mutant mice were associated with a dramatic increase of Na-K-ATPase expression, as would be expected. Experimental evidence suggests that Na-K-ATPase activity is enhanced along nephronic segments in hypertensive rats displaying CRF (16,34,36). In Milan hypertensive rats, increased Na-K-ATPase activity is linked to a higher number of pump sites with a significant increase in pretranslational ␣ and ␤ isomer mRNA levels before the onset of hypertension (34).…”

Estradiol-induced expression of Na+-K+-ATPase catalytic isoforms in rat arteries: gender differences in activity mediated by nitric oxide donors

“…Gender differences in the Na ϩ pump functional response to ACh could be related to a differential expression of the catalytic ␣-subunit isoforms of the Na ϩ -K ϩ -ATPase in rat aorta (11). Therefore, we examined total ␣ 1 and ␣ 2 protein present in aorta of male and estrous female animals.…”

“…Briefly, the aortic rings were equilibrated for 45 min in KRB (37°C) in the presence of ouabain (10 Ϫ3 M) when indicated. Finally, triplicate tissue samples were incubated in 2 ml of KRB containing 86 Rb (0.1 mCi/ml) in the presence or absence of ouabain for 20 min, as described previously (11). Transferring the aortic rings into iced KRB stopped the reaction; the tissue was then quickly washed in cold buffer and gently blotted.…”

Na+–K+–2Cl− cotransporter is implicated in gender differences in the response of the rat aorta to phenylephrine

“…The Na + pump of vascular smooth muscle cells plays a major role in the regulation of vascular tone (Bofill et al ., 1994; Clausen & Nielsen, 1994; Therien & Blostein, 2000). Recently, the enhancement of acetylcholine (ACh)‐induced relaxation observed in female rats may be in part explained by NO‐dependent increased Na + ,K + ‐ATPase activity in female vascular tissue (Palacios et al ., 2004).…”