Glucocorticoid upregulates Na-K-ATPase α- and β-mRNA via an indirect mechanism in proximal tubule cell primary cultures

Yi Chao Lee, Hsi Hui Lin, Ming Jer Tang

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Abstract

Adrenalectomy leads to the decline in the levels of renal Na-K-adenosinetriphosphatase (Na-K-ATPase) α- and β-subunit protein and mRNA. Both α- and β-mRNA, however, return to the control level within 1 h after corticosterone administration. Whether or not glucocorticoid acts directly on a specific segment of nephron to upregulate Na-K-ATPase has not been determined. Studies were undertaken in an attempt to elucidate this problem. Using primary cultures of renal proximal tubules, we found that 24-h treatment with dexamethasone augmented Na-K-ATPase activity and induced coordinate increase of α- and β-protein and mRNA abundance dependent on the doses in the range of 10-8 to 10-6 M. We further demonstrated that 24-h incubation of dexamethasone (10-7 M) enhanced Na-K-ATPase activity by 58 ± 14%, α- and β-protein abundance by 70 ± 18 and 51 ± 10%, and α- and β-mRNA levels by 87 ± 12 and 62 ± 11%, respectively. The time course studies revealed that significant increase of Na-K-ATPase activity and α- and β-protein abundance was reached within 8 h, and enhancement of α- and β-mRNA abundance was reached within 4 h of dexamethasone treatment. Pretreatment of cultured proximal tubule cells with cycloheximide (20 μg/ml) completely inhibited dexamethasone-induced increase of Na-K-ATPase α- and β-mRNA. Our results indicate that dexamethasone upregulates Na-K-ATPase in proximal tubule cells via pretranslational mechanisms, which may be mediated by proteins.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume268
Issue number5 37-5
Publication statusPublished - May 1995
Externally publishedYes

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Keywords

  • Glucocorticoids
  • Primary culture
  • Proximal tubule
  • Sodium-potassium-adenosinetriphosphatase

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

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