Aldosterone induces Ras methylation in A6 epithelia

N. F. Al-Baldawi, J. D. Stockand, O. K. Al-Khalili, G. Yue, D. C. Eaton

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Aldosterone increases Na+ reabsorption by renal epithelial cells: the acute actions (<4 h) appear to be promoted by protein methylation. This paper describes the relationship between protein methylation and aldosterone's action and describes aldosterone-mediated targets for methylation in cultured renal cells (A6). Aldosterone increases protein methylation from 7.90 ± 0.60 to 20.1 ± 0.80 methyl ester cpm/μg protein. Aldosterone stimulates protein methylation by increasing methyltransferase activity from 14.0 ± 0.64 in aldosterone-depleted cells to 31.8 ± 2.60 methyl ester cpm/μg protein per hour in aldosterone-treated cells. Three known methyltransferase inhibitors reduce the aldosterone-induced increase in methyltransferase activity. One of these inhibitors, the isoprenyl-cysteine methyltransferase-specific inhibitor, S-trans,trans-farnesylthiosalicylic acid, completely blocks aldosterone-induced protein methylation and also aldosterone-induced short-circuit current. Aldosterone induces protein methylation in two molecular weight ranges: near 90 kDa and around 20 kDa. The lower molecular weight range is the weight of small G proteins, and aldosterone does increase both Ras protein 1.6-fold and Ras methylation almost 12-fold. Also, Ras antisense oligonucleotides reduce the activity of Na+ channels by about fivefold. We conclude that 1) protein methylation is essential for aldosterone-induced increases in Na+ transport; 2) one target for methylation is p21(ras); and 3) inhibition of Ras expression or Ras methylation inhibits Na+ channel activity.

Original languageEnglish (US)
Pages (from-to)C429-C439
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number2 48-2
DOIs
StatePublished - 2000

Keywords

  • A6 cells
  • Epithelial transport
  • Protein methylation
  • Sodium transport

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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