Effect of Chronic Renal Failure on NaK-ATPase A1 and a2 mRNA Transcription in Rat Skeletal Muscle
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Bonilla, Silvia
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Effect of Chronic Renal Failure on NaK-ATPase A1 and a2 mRNA Transcription in Rat Skeletal Muscle
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Abstract
Previous studies have suggested that an alteration in the expression
of the NaK-ATPase of muscle may be an important
determinant of enhanced insulin sensitivity in chronic renal failure.
Therefore, in the present studies we have examined the
effect of uremia on the NaK-ATPase a isoforms in skeletal
muscle, at the level of mRNA expression and enzymatic activity.
The activity of the sodium pump, as measured ouabain-sensitive
'Rb/K uptake in soleus muscle, revealed a reduction in
the activity in uremia, related to the increment in plasma creatinine
values. The decrement in 86Rb uptake by the rat soleus
muscle of experimental animals was associated with changes
on NaK-ATPase gene product. Northern analysis of mRNA
revealed isoform-specific regulation of Na,K-ATPase by uremia
in skeletal muscle: a decrease of - 50% in al subunit
Na,K-ATPase mRNA, as compared to controls. The decrement
in al mRNA correlates with the decreased activity of the
Na,K-ATPase in uremia, under basal conditions and with the
almost complete inhibition of the Na,K-ATPase, of uremic tissue
by a concentration of 10-' M ouabain. Although the activity
of the a2 isoform pump was not modified by uremia, the 3.4-kb
message for this enzyme was increased 2.2-fold; this discrepancy
is discussed. Altogether these findings demonstrate that
the defective extrarenal potassium handling in uremia is at
least dependent in the expression of a1 subunit of the
Na,K-ATPase.
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URI: https://repositorio.uchile.cl/handle/2250/129075
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The American Society for Clinical Investigation, Inc. Volume 88, December 1991, 2137-2141
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