期刊
JOURNAL OF NEUROCHEMISTRY
卷 106, 期 1, 页码 37-44出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1471-4159.2008.05350.x
关键词
gamma-glutamylputrescine; gamma-lutamylspermidine; gamma-glutamyle-epsilon-lysine; bis-gamma-glutamylputrescine; CSF; Huntington disease
资金
- NIA NIH HHS [P01 AG14930, P01 AG014930-08, P01 AG014930-04, P01 AG014930] Funding Source: Medline
Transglutaminases (TGases) catalyze several reactions with protein substrates, including formation of gamma-glutamyl-epsilon-lysine cross-links and gamma-glutamylpolyamine residues. The resulting gamma-glutamylamines are excised intact during proteolysis. TGase activity is altered in several diseases, highlighting the importance of in situ enzymatic determinations. Previous work showed that TGase activity (as measured by an in vitro assay) and free gamma-glutamyl-epsilon-lysine levels are elevated in Huntington disease (HD) and that gamma-glutamyl-epsilon-lysine is increased in HD CSF. Although free gamma-glutamyl-epsilon-lysine was used in these studies as an index of in situ TGase activity, gamma-glutamylpolyamines may also be diagnostic. We have devised methods for the simultaneous determination of four gamma-glutamylamines in CSF: gamma-glutamyl-epsilon-lysine, gamma-glutamylspermidine, gamma-glutamylputrescine, and bis-gamma-glutamylputrescine and showed that all are present in normal human CSF at concentrations of similar to 150, 670, 40, and 240 nM, respectively. The high gamma-glutamylspermidine/gamma-glutamylputrescine and gamma-glutamylspermidine/bis-gamma-glutamylputrescine ratios presumably reflect in part the large spermidine to putrescine mole ratio in human brain. We also showed that all four gamma-glutamylamines are elevated in HD CSF. Our findings support the hypotheses that (i) gamma-glutamylpolyamines are reflective of TGase activity in human brain, (ii) polyamination is an important post-translational modification of brain proteins, and (iii) TGase-catalyzed modification of proteins is increased in HD brain.
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