Disease relevance of NSC22879

• Of embryos treated with 50 microliters of the teratogenic dose (200 mM D,L-homocysteine or 100 mM L-homocysteine thiolactone) on incubation days 0, 1, and 2 and harvested at 53 h (stage 14), 27% showed neural tube defects [1].
• In a separate group of alpha- and beta-receptor-blocked animals that received an infusion of L-homocysteine thiolactone during hypoxia, there was no difference in tissue S-adenosylhomocysteine levels compared with those of normoxic controls [2].
• Here we show that isoleucyl- and leucyl-tRNA synthetases also edit homocysteine by cyclizing it to homocysteine thiolactone in the bacterium Escherichia coli [3].
• Irreversible inhibition of lysyl oxidase by homocysteine thiolactone and its selenium and oxygen analogues. Implications for homocystinuria [4].
• Modification of fibrinogen by homocysteine thiolactone increases resistance to fibrinolysis: a potential mechanism of the thrombotic tendency in hyperhomocysteinemia [5].

Psychiatry related information on NSC22879

• Considering the opposing effects on butyrylcholinesterase of homocysteine thiolactone and cholinesterase inhibitors, understanding how these molecules alter this enzyme may provide new insights in the management of dementia [6].

High impact information on NSC22879

• The inclusion of homocysteine thiolactone, a metabolic precursor of methionine, in the methionine-deficient medium inhibited the derepression in normal human fibroblasts but augmented the derepression in fully transformed fibroblasts [7].
• CRF-induced increases in phospholipid methylation and ACTH secretion were reduced when cells were treated with the phospholipid methyltransferase inhibitors 3-deazaadenosine and L-homocysteine thiolactone [8].
• Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosis [9].
• In medium with L-homocysteine thiolactone, 5-methyltetrahydrofolate, and dialyzed serum, cyanocobalamin [c-lactam] caused cell death, reversible by additional vitamin B12 [10].
• Following 30 minutes of coronary artery ligation and infusion of L-homocysteine thiolactone (10 mumol/kg/min i.v.) SAH levels increased from 1.3 (control) to 3.3 nmoles/g in the nonischemic and to values over 100 nmoles/g in the ischemic region [11].

Chemical compound and disease context of NSC22879

• The concentration of gamma-aminobutyrate (GABA) and the activity of glutamate decarboxylase and GABA-transaminase were measured in extracts of mouse brain before the onset and during the course of generalized seizures induced by systemic administration of homocysteine thiolactone [12].
• Tiagabine was administered to cobalt-lesioned rats in which status epilepticus was induced by injection of homocysteine thiolactone [13].

Biological context of NSC22879

• Normal cells incorporated homocysteine thiolactone in peptide linkage, but homocysteine thiolactone was released by acid hydrolysis [14].
• Addition of homocysteine thiolactone (Hcy-tl) to the medium enhanced AdoHcy (and c3AdoHcy) accumulation but did not affect the cell growth at concentrations of inhibitor less than 10 microM [15].
• Substrate specificity studies suggest that homocysteine thiolactone is a likely natural substrate of this enzyme [16].
• In competition-based ELISAs, homocysteine thiolactone-treated LDL competed for binding with the antiserum, as the 50% inhibitory concentration was approximately 10 microg/ml [17].
• Homocysteine thiolactone (tHcy) is deemed a risk factor for cardiovascular diseases and strokes, presumably because it acylates the side chain of protein lysine residues ("N-homocysteinylation"), thereby causing protein damage and autoimmune responses [18].

Anatomical context of NSC22879

• We showed previously that homocysteine thiolactone (HcyT) is a potent inducer of apoptosis in HL-60 cells [19].
• The data indicate that methionyl-tRNA synthase is involved in synthesis of homocysteine thiolactone in CHO cells, thereby extending this important proofreading mechanism to mammalian cells [20].
• Homocysteine thiolactone causes convulsions when administered to animals, and has recently been reported to have excitatory effects on neurons in the central nervous system [21].
• Homocysteine thiolactone and 3-deazadenosine, inhibitors of transmethylation, inhibited incorporation of methyl-3H into phospholipids at 3.5 h by approximately 90% and also inhibited LPC-induced acrosome reactions by 60% [22].
• Although the presence of 3-deazaadenosine and homocysteine thiolactone reduced IgE-dependent histamine release, treatment with these compounds elevated mast cell cyclic AMP levels [23].

Associations of NSC22879 with other chemical compounds

• TLC of the amino acid released from tRNA charged with [14C]homocysteine, revealed radioactivity in homocysteine, methionine and homocysteine thiolactone, indicating a conversion of tRNA-attached homocysteine to methionine [24].
• Complete blockage of the methylation of phospholipid by a mixture of erythro-9-[2-hydroxy-3-nonyl]adenine, adenosine, and L-homocysteine thiolactone markedly inhibited the activation of phospholipase A2 by the S component [25].
• Amylase secretion stimulated either by carbamoylcholine or by isoprenaline could not be affected by inhibitors of methyltransferases (3-deaza-adenosine alone or plus homocysteine thiolactone) under conditions where phospholipid methylation was strongly inhibited [26].
• Inhibition of phospholipid methylation to 75% of normal with homocysteine thiolactone did not affect luteinizing hormone-stimulated androgen production [27].
• Taken together, our findings suggest that antioxidant pretreatment with NAC, Vit C or Vit E exerts more beneficial effects than folate on reducing apoptotic cell damage induced by homocysteine thiolactone [19].

Gene context of NSC22879

• Other thiol-containing compounds, including l-homocysteine thiolactone and DTT, induced VEGF expression 7.9- and 8.8-fold [28].
• Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation [29].
• It is concluded that hyperhomocysteinemia may exert its adverse effects, in part, through the metabolite of homocysteine, homocysteine thiolactone, which is capable of altering the activity of human cholinesterases, the most pronounced effect being BuChE activation [30].
• Homocysteine-induced modification of HDL is mediated by homocysteine-thiolactone, and can be prevented by a calcium-dependent thiolactonase/paraoxonase [31].
• Multi-copy expression of hsrA was shown to lead to accumulation of homocysteine, which is predicted to cause an increase in homocysteine thiolactone (HCTL) levels [32].

Analytical, diagnostic and therapeutic context of NSC22879

• Further purification of plasma homocysteine-thiolactone is achieved by high-performance liquid chromatography on a cation exchange microbore column [33].
• Quantitative assay of plasma homocysteine thiolactone by gas chromatography/mass spectrometry [34].
• The assay involves separation of homocysteine-thiolactone from macromolecules by ultrafiltration [35].
• Seizures were induced in 7-day-old rats by intraperitoneal injection of DL-homocysteine thiolactone [36].
• Homocysteine thiolactone adducts were determined with ELISA [37].

References