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 language | English (US) |
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Pages (from-to) | C429-C439 |
Journal | American Journal of Physiology - Cell Physiology |
Volume | 279 |
Issue number | 2 48-2 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- A6 cells
- Epithelial transport
- Protein methylation
- Sodium transport
ASJC Scopus subject areas
- Physiology
- Cell Biology