S-adenosyl-l-homocysteine hydrolase regulates aldosterone-induced Na+ transport

James D. Stockand, Nabil F. Al-Baldawi, Otor K. Al-Khalili, Roger T. Worrell, Douglas C. Eaton

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Aldosterone-induced Na+ reabsorption, in part, is regulated by a critical methyl esterification; however, the signal transduction pathway regulating this methylation remains unclear. The A6 cell line was used as a model epithelia to investigate regulation of aldosterone-induced Na+ transport by S-adenosyl-L-homocysteine hydrolase (SAHHase), the only enzyme in vertebrates known to catabolize S-adenosyl-L-homocysteine (SAH), an end product inhibitor of methyl esterification. Sodium reabsorption was decreased within 2 h by 3-deazaadenosine, a competitive inhibitor of SAHHase, with a half inhibitory concentration between 40 and 50 μM. Aldosterone increased SAH catabolism by activating SAHHase. Increased SAH catabolism was associated with a concomitant increase in S-adenosylmethionine catabolism. Moreover, SAH decreased substrate methylation. Antisense oligonucleotide complementary to SAHHase mRNA decreased SAHHase activity and Na+ current by approximately 50%. Overexpression of SAHHase increased SAHHase activity and dependent substrate methyl esterification. Whereas basal Na+ current was not affected by overexpression of SAHHase, aldosterone-induced current in SAHHase- overexpressing cells was significantly potentiated. These results demonstrate that aldosterone induction of SAHHase activity is necessary for a concomitant relief of the methylation reaction from end product inhibition by SAH and the subsequent increase in Na+ reabsorption. Thus, regulation of SAHHase activity is a control point for aldosterone signal transduction, but SAHHase is not an aldosterone-induced protein.

Original languageEnglish (US)
Pages (from-to)3842-3850
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number6
DOIs
StatePublished - Feb 5 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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