An enzyme hydrolyzing methylated inhibitors of nitric oxide synthase is present in circulating human red blood cells

Ellen S. Kang, Taylor B. Cates, Dyette N. Harper, Thomas M. Chiang, Linda Myers, Sergio R. Acchiardo, Masumi Kimoto

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

NG,NG-dimethyl-L-arginine (asymmetric dimethylarginine or ADMA) and NG-monomethyl-L-arginine (L-NMMA) are post-translationally synthesized amino acids of nuclear proteins. Upon release during protein turnover, they are not used in protein synthesis, but are excreted or metabolized by dimethylarginine dimethylaminohydrolase (DDAH) found in many tissues. DDAH is present in monocytic and polynuclear cells of blood, but no report has appeared of its presence in red blood cells (RBCs). Because methylated arginines can inhibit nitric oxide synthase (NOS) and elevations are reported in several diseases, we explored whether RBCs express this enzyme. DDAH is present in RBCs as supported by hydrolysis of both ADMA and L-NMMA, but not symmetric dimethyl-arginine, and by immunoprecipitation/Western blot using a specific monoclonal antibody to human DDAH. In a pilot study of end-stage renal disease (ESRD) patients, RBC DDAH activity with ADMA as substrate correlated inversely with age (p = 0.005) and enzyme activities were higher in patients with greater diastolic blood pressure drops during hemodialysis (p = 0.02). Similar correlations were found with white cell DDAH activity. Thus, human RBCs can hydrolyze methylated arginines. These findings indicate the RBC could be used to assess the status of DDAH in various disease states.

Original languageEnglish (US)
Pages (from-to)693-707
Number of pages15
JournalFree Radical Research
Volume35
Issue number6
DOIs
StatePublished - Jan 1 2001

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Nitric Oxide Synthase
Blood
Erythrocytes
Cells
omega-N-Methylarginine
Enzymes
Arginine
Blood Pressure
Blood pressure
Enzyme activity
Nuclear Proteins
dimethylargininase
Immunoprecipitation
Chronic Kidney Failure
Pressure drop
Renal Dialysis
Hydrolysis
Blood Cells
Proteins
Western Blotting

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

An enzyme hydrolyzing methylated inhibitors of nitric oxide synthase is present in circulating human red blood cells. / Kang, Ellen S.; Cates, Taylor B.; Harper, Dyette N.; Chiang, Thomas M.; Myers, Linda; Acchiardo, Sergio R.; Kimoto, Masumi.

In: Free Radical Research, Vol. 35, No. 6, 01.01.2001, p. 693-707.

Research output: Contribution to journalArticle

Kang, Ellen S. ; Cates, Taylor B. ; Harper, Dyette N. ; Chiang, Thomas M. ; Myers, Linda ; Acchiardo, Sergio R. ; Kimoto, Masumi. / An enzyme hydrolyzing methylated inhibitors of nitric oxide synthase is present in circulating human red blood cells. In: Free Radical Research. 2001 ; Vol. 35, No. 6. pp. 693-707.
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