Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CYSTAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1993

Benextramine-neuropeptide Y receptor interactions: contribution of the benzylic moieties to [3H]neuropeptide Y displacement activity.

Analogs of N,N'-bis[6-[(2-methoxybenzyl)amino]hex-1-yl]cystamine (benextramine, BXT, 2) were synthesized using solution-phase peptide synthesis methodology and analyzed for activity in displacing specifically bound 1 nM N-[propionyl-3H]neuropeptide Y([3H]NPY) from benextramine-sensitive neuropeptide Y (NPY) binding sites in rat brain. Our new synthetic approach to these analogs began with the acylation of cystamine with the N-hydroxysuccinimide ester of tert-butyloxycarbonyl (t-Boc) protected 6-aminohexanoic acid, followed by deprotection of the t-Boc groups with 4 N HCl in dioxane. Acylation of this symmetric diamine with N-hydroxysuccinimide esters of appropriately substituted benzoic acids, followed by reduction of the resultant tetraamides with diborane in refluxing THF, afforded the target compounds. The BXT analog lacking the benzylic group (i.e., compound 11) had no [3H]NPY displacement activity at concentrations up to 1.4 x 10(-3) M. The 9-fold range in activities observed for the ortho, meta, and para regioisomers of the methoxy, chloro, and hydroxy benextramine analogs at benextramine-sensitive NPY rat brain binding sites does not differ from the range of potencies observed at alpha-adrenoceptors. However, the order of potencies at [3H]NPY sites differs from the order of potencies at alpha-adrenoceptors, with the m-methoxyphenyl (9a), m-hydroxyphenyl (10b), and 2-naphthyl (9f) analogs being the most active at [3H]NPY binding sites. The present results demonstrate the importance of the benzylic moiety for BXT's NPY antagonist activity, and suggest that the BXT binding site on the NPY receptor is significantly distinct from that on the alpha-adrenoceptor.

Adrenergic alpha-Antagonists↗
PubMed1998

Nitric oxide as neuromodulator of sympathetic transmission in rat vas deferens.

1. Electrical field stimulation (EFS) of muscle strips in vitro elicited a tetrodotoxin (TTX)-sensitive biphasic contractile response consisting of a phasic component followed by a tonic one. 2. The amplitude of both components of the response was impaired by N omega-nitro-L-arginine and potentiated by sodium nitroprusside. Cystamine caused a reduction in amplitude of both phasic and tonic components of the response to EFS. Neither N omega-nitro-L-arginine, sodium nitroprusside, nor cystamine induced changes in the resting muscle tone, or in the contractile response to exogenous agonists ATP and noradrenaline (NA). 3. The nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, induced a reduction in amplitude of both components of the response to EFS. 4. These results reveal a facilitatory prejunctional modulatory role for nitric oxide in sympathetic neurotransmission in rat vas deferens. Endogenous nitric oxide released in the extracellular space is presumed to potentiate neurotransmission by acting at prejunctional level via cGMP.

Animals↗
PubMed1999

Transglutaminase activity in equine strongyles and its potential role in growth and development.

Transglutaminases (E.C. 2.3.3.13) are a family of Ca(2+)-dependent enzymes that stabilize protein structure by catalyzing the formation of isopeptide bonds. A novel form of transglutaminase has been identified and characterized that seem to play an important role in growth, development, and molting in adult and larval stages of filarial nematodes. The aim of this study was to identify the ubiquitous nature of this enzyme in other nematodes and to measure its significance to larval growth, molting, and development. For this purpose, equine Strongylus spp. were used. Activity of this enzyme was identified in extracts of larvae and adults of Strongylus vulgaris, S. edentatus, Parascaris equorum and Cylicocyclus insigne. The significance of transglutaminase in the early growth and development of Strongylus vulgaris, S. edentatus and S. equinus was tested by adding specific inhibitors, monodansylcadaverine (MDC) or cystamine (CS), to in vitro cultures of third (L3) and fourth stage larvae (L4). The viability, molting and growth of these nematode species were affected by both inhibitors. Cystamine promoted abnormal development of Strongylus edentatus L3, resulting in an aberrant expansion of the anterior end. Addition of these inhibitors to cultures of L4 also reduced growth of the three species. The results indicated that transglutaminase is present in a wide array of nematode parasites and may be important in growth and development of their larval stages.

Animals↗
PubMed1981

Increase in proliferative markers after inhibition of transglutaminase.

Cystamine inhibited transglutaminase activity (R-glutaminyl-peptide:amine gamma-glutamyltransferase, EC 2.3.2.13) of proliferating WI-38 cells in a dose-dependent manner over the concentration range 0.005-0.25 mM when added to the culture medium. The epsilon-(gamma-glutamyl)lysine content in the cells was decreased and several proliferation markers were enhanced. "Non-mitotic" cells were stimulated by cystamine (about 25% of that observed with 10% fetal bovine serum) to undergo DNA synthesis with subsequent increases in nuclei number. Numerous other disulfides, thiols, and amines were ineffective when added to culture medium. The findings are supportive of the concept that growth control involves a relationship between isopeptide crosslinks and proliferation.

Cell Division↗
PubMed1996

Specifically targeted modification of human aldose reductase by physiological disulfides.

Aldose reductase is inactivated by physiological disulfides such as GSSG and cystine. To study the mechanism of disulfide-induced enzyme inactivation, we examined the rate and extent of enzyme inactivation using wild-type human aldose reductase and mutants containing cysteine-to-serine substitutions at positions 80 (C80S), 298 (C298S), and 303 (C303S). The wild-type, C80S, and C303S enzymes lost >80% activity following incubation with GSSG, whereas the C298S mutant was not affected. Loss of activity correlated with enzyme thiolation. The binary enzyme-NADP+ complex was less susceptible to enzyme thiolation than the apoenzyme. These results suggest that thiolation of human aldose reductase occurs predominantly at Cys-298. Energy minimization of a hypothetical enzyme complex modified by glutathione at Cys-298 revealed that the glycyl carboxylate of glutathione may participate in a charged interaction with His-110 in a manner strikingly similar to that involving the carboxylate group of the potent aldose reductase inhibitor Zopolrestat. In contrast to what was observed with GSSG and cystine, cystamine inactivated the wild-type enzyme as well as all three cysteine mutants. This suggests that cystamine-induced inactivation of aldose reductase does not involve modification of cysteines exclusively at position 80, 298, or 303.

Aldehyde Reductase↗
PubMed2002

Transglutaminase activity is involved in Saccharomyces cerevisiae wall construction.

Transglutaminase activity, which forms the interpeptidic cross-link N(epsilon)-(gamma-glutamyl)-lysine, was demonstrated in cell-free extracts of Saccharomyces cerevisiae by incorporation of [(14)C]lysine into an exogenous acceptor, N,N'-dimethylcasein. Higher levels of the activity were present in the cell wall, which also contained endogenous acceptors. The enzyme activity in the wall was inhibited by cystamine, a known inhibitor of transglutaminase, and by EDTA, indicating a cation-dependent activity. After the endogenous wall acceptors were labelled radioactively by transglutaminase, extraction with SDS solubilized about 50% of the total radioactivity, while Zymolyase and chitinase each released a further 3%. The proteins solubilized by SDS had molecular masses less than 50 kDa, whereas the material released by Zymolyase or chitinase had molecular masses greater than 180 kDa, suggesting a precursor-product relationship. Cystamine inhibited the growth of several strains of S. cerevisiae. Treated cells showed increased sensitivity to Zymolyase and appeared as protoplasts, indicating gross alterations in the cell wall. These data suggest that transglutaminase may be involved in the formation of covalent cross-links between wall proteins during wall construction.

Cell Extracts↗
PubMed2004

Pigment-lightening effect of N,N'-dilinoleylcystamine on human melanoma cells.

BACKGROUND: Cystamine and linoleic acid have been reported to reduce melanin synthesis in vitro and in vivo. N,N'-dilinoleylcystamine (DLC) is a compound of cystamine and linoleic acid connected by an ester bond. OBJECTIVES: To investigate the effects of DLC on melanin synthesis using cultured human melanoma cells. METHODS: Levels of total melanin, eumelanin and phaeomelanin, tyrosinase protein and tyrosinase activity in situ were measured in HM3KO melanoma cells. Changes in degree of pigmentation were quantified by image analysis and compared with absorbance values. Tyrosinase from HM3KO cells was used to measure the direct effect of DLC on DOPA and DOPAchrome production. RESULTS: At concentrations of 1.4-14 micromol L-1, DLC reduced the pigmentation of HM3KO melanoma cells but did not affect cell growth. The visual decrease in pigmentation produced by DLC was more dramatic than the decrease in total melanin content as measured by absorbance at 500 nm. DLC treatment decreased eumelanin synthesis and increased phaeomelanin synthesis in HM3KO melanoma cells. An in situ tyrosinase assay showed that DLC inhibited tyrosinase activity, as well as the level of tyrosinase protein. CONCLUSIONS: These results suggest that DLC has pigment-lightening effects on HM3KO melanoma cells, produced by reducing the level of eumelanin while increasing the level of phaeomelanin.

Blotting, Western↗
PubMed1991

Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro.

The possible involvement of transglutaminase-catalyzed reactions in survival of adult worms, microfilariae (mf), and infective larvae of the filarial parasite Brugia malayi was studied in vitro by using the specific pseudosubstrate monodansylcadaverine (MDC) and the active-site inhibitors cystamine or iodoacetamide. These inhibitors significantly inhibited parasite mobility in a dose-dependent manner. This inhibition was associated with irreversible biochemical lesions followed by filarial death. A structurally related, inactive analog of MDC, dimethyldansylcadaverine, did not affect the mobility or survival of the parasites. Adult worms failed to release mf when they were incubated in the presence of MDC or cystamine, and this inhibitory effect on mf release was concentration dependent. Similar embryostatic and macrofilaricidal effects of MDC were observed in Acanthocheilonema viteae adult worms. These studies suggest that transglutaminase-catalyzed reactions may play an important role in the growth, development, and survival of filarial parasites.

Animals↗
PubMed1983

Reduction of the secretory response to Escherichia coli heat-stable enterotoxin by thiol and disulfide compounds.

We examined the effects of disulfide and thiol compounds on Escherichia coli heat-stable enterotoxin (ST) and cyclic GMP-induced secretion. Both cystamine and cystine (disulfide compounds) reduced the secretory responses to submaximal doses of ST in suckling mice (at 0.5 mumol per mouse) and reduced ST activation of guanylate cyclase (by 33 to 73% at 1 mM). In higher doses, cystamine completely eradicated a maximally effective ST dose as well. In addition, the sulfhydryl (thiol) compounds cysteamine, cysteine, and acetylcysteine strikingly reduced the secretory response and the guanylate cyclase response to ST. Neither the disulfide nor the thiol compounds tested reduced cyclic GMP-induced secretion. These studies suggest that disulfide and thiol compounds both block ST-induced secretion before its activation of guanylate cyclase. Taken with the work of others, these findings suggest that disulfide compounds may alter the oxidation reduction state of a cell or act directly on the guanylate cyclase enzyme, whereas thiol compounds may inactivate ST itself by breaking its disulfide bridges, or it may alter guanylate cyclase activation by ST. Both families of compounds deserve further consideration among potential antisecretory agents for application in the control of ST-induced diarrhea.

Acetylcysteine↗
PubMed1996

Are acantholysis and transglutaminase inhibition related phenomena?

BACKGROUND: The loss of intercellular cohesion among keratinocytes (acantholysis) may be considered the histologic marker of pemphigus. Many drugs, especially thiol drugs, proved to be able to provoke in vitro acantholysis by biochemical mechanisms interfering with the disulfide and thiol group balance. As to nonthiol drugs, the pathomechanism of acantholysis is still unexplained. OBJECTIVE: To explain the molecular mechanism of enalapril-induced acantholysis a potential link between transglutaminase (TGase) activity and the effects of this drug was investigated. METHODS: TGase activity in extracts from human breast skin cultured in the presence of thiopronine, captopril and enalapril were evaluated in vitro. The acantholytic potential of cystamine, a known TGase inhibitor, was also investigated. RESULTS: Enalapril, the most powerful acantholytic drug in vitro, was found to inhibit both the purified enzyme and the TGase activity in the extracts from cultured human breast skin explants. Kinetic studies showed that enalapril inhibition was competitive with respect to the amino acceptor substrate and uncompetitive with respect to the amino donor substrate. Moreover, an acantholytic effect of cystamine on explants of normal human skin was shown. CONCLUSIONS: These results suggest that acantholysis and the inhibition of TGase activity could be two related phenomena.

Acantholysis↗
PubMed1988

Mucopolysaccharidosis type I subtypes. Presence of immunologically cross-reactive material and in vitro enhancement of the residual alpha-L-iduronidase activities.

The enzymatic and immunologic properties of the defective residual alpha-L-iduronidase activities were investigated in fibroblast extracts from the three subtypes of mucopolysaccharidosis type I, Hurler (MPS IH), Scheie (MPS IS), and Hurler-Scheie (MPS IH-S) diseases. Using 4-methylumbelliferyl-alpha-L-iduronide (4MU-alpha-Id), the activities in fibroblast extracts from all three subtypes were less than 0.1% of normal. Rocket immunoelectrophoresis with monospecific rabbit anti-human alpha-L-iduronidase polyclonal antibodies, as well as immunoblots using a monoclonal antibody, revealed the presence of cross-reactive immunologic material (CRIM) in extracts prepared from each subtype. When the samples were equalized for beta-hexosaminidase A activity, 38-105% of normal enzyme protein was detected. The sequential addition of cystamine, MgCl2 and pyridoxal phosphate increased the residual 4MU-alpha-Id activities in subtype extracts up to about 35% of normal mean fibroblast activity. Cystamine, MgCl2 or pyridoxal phosphate alone enhanced the residual activities two- to fourfold, whereas the sequential addition of all three compounds was required for maximal effect. Of the six B6 vitamers evaluated, only the negatively charged forms, pyridoxamine (PLN), pyridoxamine phosphate (PNP), and pyridoxal phosphate (PLP), stimulated the residual activities. The addition of dermatan sulfate or heparan sulfate to the subtype extracts, followed by treatment with the effector compounds, similarly inhibited both the normal and enhanced MPS I activities. Heat inactivation experiments confirmed the fact that the mutant iduronidase activity was reconstituted and that the observed increase in enzymatic activity was not an artifact of the fluorogenic assay. These results suggest that the presence of certain thiol reducing agents, divalent cations and negatively charged B6 vitamers can alter the conformation of the mutant alpha-L-iduronidase in vitro such that the hydrolysis of 4MU-alpha-Id is enhanced into the heterozygote range.

Animals↗
PubMed1987

Cysteamine-induced decrease of somatostatin in rat brain synaptosomes in vitro.

The mechanism of somatostatin depletion induced by cysteamine [2-mercaptoethylamine (CySH)] was studied in isolated nerve endings (synaptosomes) from rat brain in vitro. A dose-dependent reduction of somatostatin-like immunoreactivity (SLI) was observed which reached its maximal extent (41%) at a concentration of 300 microM CySH after 1-5 min. There was no release of somatostatin into the incubation medium. CySH at concentrations of up to 10 mM did not interfere in the RIA. Among a variety of compounds, structurally related to CySH 4-aminothiophenol, 2-aminothiophenol and N,N-dimethylaminothiol exhibited the highest efficacy in decreasing somatostatin (60%, 50%, 30%, respectively, at 10 mM and 10 min). The disulfide form of CySH cystamine and dimercaprol resulted in about 15% reduction after 10-min incubation, whereas taurine, alanine, cysteine, and mercaptoethanol were inactive. A saturable, sodium-dependent uptake process was found for the disulfide form of [35S]CySH cystamine [Michaelis-Menten constant (Km) = 18.6 microM, maximum velocity (Vmax) = 2.3 nmol/mg protein X 3 min) which was inhibited by cysteine (87% at 1 mM). [35S]CySH, at concentrations of 20 microM or less, was not stable in buffer solution. It underwent considerable nonenzymatic conversion into its dimeric form (60% at 37 C and 3 min), however it exhibited the same kinetic data for its uptake. Size exclusion HPLC of purified hypothalamic synaptosomes revealed a major SLI peak coeluting with synthetic somatostatin-14 and two minor peaks representing somatostatin-28 and a 13,000 mol wt protein. The three molecular forms of somatostatin were reduced to varied extent by CySH (somatostatin-14 by about 70%, somatostatin-28 by 15%, and the high mol wt form by 30%). Our experiments suggest that high affinity uptake of CySH may precede its action in decreasing somatostatin levels. Increased release or inhibition of synthesis of somatostatin have been excluded as possible mechanisms. It is suggested that SLI is equally affected in nerve endings and in perikarya.

Animals↗
PubMed1981

The effect of sulfhydryl blocking agents on the uptake of L-carnitine in an established human cell line (CCL 27).

The effect of sulfhydryl blocking agents on the active transport of L-carnitine into cells from an established cell line from human heart was studied. N-ethylmaleimide (MalNEt), 5,5-dithiobis-(2-nitrobenzoic acid) (Nbs2), parachloromercuribenzoate (ClHgBzO-) and cystamin all reduced the uptake of L-carnitine considerably. This was not due to a general membrane injury as judged by the trypan blue dye exclusion test. The inhibition caused by N-ethylmaleimide was irreversible, while that of Nbs2, ClHgBzO- and cystamin could be reversed by dithiothreitol. Excess L-carnitine in the medium exerted a small protective effect against the inhibition of Nbs2, but had no effect against the inhibition of the other agents. Neither could ClHgBzO- protect the uptake mechanism against the irreversible inhibition of N-ethylmaleimide. We conclude that the observations reflect the existence of a multitude of different SH-groups, and that some of these are essential for the cellular uptake of L-carnitine.

Biological Transport, Active↗
PubMed1982

Resistance to prolonged irradiation in mice influenced by thyroid hormones and chemical radiation protectors.

After the end of 10 and 21 days' treatment of mice with dried thyroid gland (0.6 g/100 g diet) the effect of some radiation protectors against prolonged irradiation (38 mGy/min) increased. The combination of propranolol, phenobarbital and cystamine was more effective than a mixture of cystamine and 5-methoxytryptamine both in mice fed on a normal and a thyroid gland diet. A reduced oxygen consumption after the application of protectors reflected the degree of protection. The number of thrombocytes in peripheral blood increased after the end of thyroid treatment, which indicated a possible shift in the differentiation of stem cells in favour of megakaryocytes.

5-Methoxytryptamine↗
PubMed1991

Ultrastructure of erythroblast mitochondria in mice treated with mixtures of radioprotectors.

Unirradiated mice were given i.p. a mixture of mexamine (20 mg/kg body weight) and AET (150 mg/kg body weight) or mexamine (20 mg/kg body weight) and cystamine (150 mg/kg body weight). Acute effects of these mixtures of radioprotective agents on the ultrastructure of basophilic and polychromatic bone marrow erythroblast mitochondria were studied. One hour after injecting mice with above-mentioned mixtures, statistically significant differences in the size of mitochondria were found between control mice and mice given a mixture of mexamine and cystamine. The differences in the number of dilated cristae per micron 2 of the mitochondrion area between control mice and both experimental groups given mixtures of radioprotective agents were also statistically significant. Thus it was proved that also mixtures of radioprotectors induced acute ultrastructural changes of mitochondria which were so far described only after treating mice with only one radioprotective agent.

5-Methoxytryptamine↗
PubMedDate not supplied

[Effect of radioprotectars from various chemical compound classes on dynamic work capacity and carbohydrate metabolism].

The influence of radioprotectors cystamine, mexamine and gammaphos on the physical performance capacity and carbohydrate metabolism was subjected to a comparative study. Cystamine and mexamine were found to lower the capacity of the animals to endure physical loads, this being attended by falling stocks of glycogen in the liver and muscles and a rising level of the blood lactate and pyruvate in comparison with controls. Gammaphos has no effect on the performance capacity of the animals and carbohydrate metabolism.

5-Methoxytryptamine↗
PubMedDate not supplied

[Radioprotective effect of drug combinations on the small intestine].

The study of the radioprotective effect of complexes containing small amounts of cystamine or gammaphos mixed with mexamine, gutimine and ethyrone on mouse small intestine showed high efficiency of the drugs as determined by cellularity and DNA-synthesizing activity of intestinal epithelium. This is connected with the influence of the complex mexamine + gutimine + ethyrone on the pharmacodynamics and pharmacokinetics of cystamine and gammaphos.

Animals↗
PubMed1981

Reversible inactivation of guanylate cyclase by mixed disulfide formation.

Highly purified preparations of guanylate cyclase from rat lung were inactivated by several disulfide compounds in a time- and dose-dependent manner. Cystamine and cystine were the most potent disulfides tested, but other compounds which contained the cysteamine moiety (NH2CH2CH2S-), including pantethine and oxidized coenzyme A, were also able to partially inactivate the enzyme. In addition to the decrease in basal activity (measured with either Mg2+-GTP or Mn2+-GTP), disulfide-inhibited enzyme was activated to a lesser extent by nitric oxide. Treatment with dithiothreitol or other reducing agents restored basal activity and increased the level of cGMP production following nitric oxide activation. Control enzyme samples exhibited a single GTP Km of 25 microM or 150 microM with Mn2+ or Mg2+, respectively. However, cystamine-treated enzyme showed these same Km values as well as an additional GTP Km of 2 to 3 microM using either metal ion as cofactor. When [35S]cystine was incubated with purified enzyme, radioactivity was incorporated into the trichloroacetic acid-precipitable protein, and the counts were released following dithiothreitol treatment. In addition, [35S]cystine-labeled enzyme co-migrated with native guanylate cyclase on nondenaturing polyacrylamide gels. These data indicate that mixed disulfides can be formed between guanylate cyclase and certain naturally occurring compounds, and that disulfide formation leads to a reversible loss of enzyme activity.

Animals↗