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At least 325 records · Page 18Linked to original sources
PubMed2000

Pantetheinase activity of membrane-bound Vanin-1: lack of free cysteamine in tissues of Vanin-1 deficient mice.

Pantetheinase (EC 3.5.1.-) is an ubiquitous enzyme which in vitro has been shown to recycle pantothenic acid (vitamin B5) and to produce cysteamine, a potent anti-oxidant. We show that the Vanin-1 gene encodes pantetheinase widely expressed in mouse tissues: (1) a pantetheinase activity is specifically expressed by Vanin-1 transfectants and is immunodepleted by specific antibodies; (2) Vanin-1 is a GPI-anchored pantetheinase, and consequently an ectoenzyme; (3) Vanin-1 null mice are deficient in membrane-bound pantetheinase activity in kidney and liver; (4) in these organs, a major metabolic consequence is the absence of detectable free cysteamine; this demonstrates that membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. Since the Vanin-1 molecule was previously shown to be involved in the control of thymus reconstitution following sublethal irradiation in vivo, this raises the possibility that Vanin/pantetheinase might be involved in the regulation of some immune functions maybe in the context of the response to oxidative stress.

Amidohydrolases↗
PubMed2002

The ability of hippocampal CA1 area for induction of long-term potentiation is persistently reduced by prior treatment with cysteamine: an in vitro study.

Using field potential recording in the CA1 region of hippocampal slices from rats injected with cysteamine (200 mg/kg, s.c.), changes in activity and plasticity of Schaffer collateral-CA1 pyramidal cell synapses were examined. Extracellular field potential recording prior to and following either theta-pattern primed bursts (PBs), perfusion with low Mg(2+) or with high Ca(2+), indicated long-term potentiation (LTP) of population spikes amplitude (PSA). The extent of LTP of PSA was significantly lower in cysteamine-treated rats. It is concluded that cysteamine can entail lasting modifications in susceptibility of hippocampal CA1 for synaptic plasticity induced by tetanus. Similarly, disability in function of CA1 synapses can be traced by other protocols of LTP induction. The relevancy of the results to the facilitatory role of endogenous somatostatin in the function of Schaffer collateral-CA1 pyramidal cell synapses is also discussed.

Animals↗
PubMed1997

Influence of the neuropeptide somatostatin on the development of dendritic morphology: a cysteamine-depletion study in the rat auditory brainstem.

We investigated the functional role of somatostatin during early ontogeny of the brain, when the neuropeptide as well as its receptors are heavily expressed in the auditory brainstem. Rat pups received a daily injection of cysteamine which, when applied at low concentrations, most selectively depletes somatostatin. Neurons from the lateral superior olive, an auditory brainstem nucleus which transiently receives a dense somatostatinergic input, were intracellularly labeled at postnatal day 14 or 18. The dendritic morphology of these neurons was then analyzed quantitatively and compared with neurons from controls. Cysteamine treatment induced a reduction of the number of dendritic end points by more than 50%. At postnatal day 14, for example, controls and somatostatin-depleted animals had an average of 58 and 28 end points, respectively. The number of primary dendrites was also significantly reduced by cysteamine. In contrast, the size of the somata, the orientation of the dendritic trees within the lateral superior olive, the dendritic areas, and the cross-sectional size of the lateral superior olive were not altered. These results indicate that somatostatin depletion during early development has profound effects on the maturation of dendritic morphology. The selective influence on the dendritic trees suggests that somatostatin acts as an endogenous trophic peptide and promotes the achievement of dendritic complexity.

Animals↗
PubMed1998

Determination of total cysteamine in human serum by a high-performance liquid chromatography with fluorescence detection.

A convenient, reliable and rapid method for determination of total cysteamine in human plasma by high-performance liquid chromatography with fluorescence detection is reported. This assay involves reduction of samples with dithiothreitol, derivatization of total cysteamine by addition of monobromobimane and protein precipitation by perchloric acid. The calibration curve was linear in the range 2-150 nmol ml-1 and the detection limit was 0.5 nmol ml-1. This method was successfully applied for a pharmacokinetic study of three cysteamine derivatives in healthy volunteers without any interference from coexisting substances.

Biological Availability↗
PubMed1997

Effects of pregnancy in rats on cysteamine-induced peptic ulcers: role of progesterone.

After mating with a sexually active male, groups of female Sprague-Dawley rats were injected with cysteamine (400 mg/kg, subcutaneously) at day 0 (controls), day 5 (early-stage pregnancy), and day 18 (late-stage pregnancy) of pregnancy. In contrast to late-stage pregnancy rats, early-stage pregnancy animals showed a decrease of cysteamine-induced gastroduodenal lesions. When subjected to cysteamine injection, both nonpregnant female and male rats treated for eight days with progesterone (300 microg/rat, subcutaneously) showed a reduced incidence of gastroduodenal lesions. No effect was found in animals pretreated with 17beta-estradiol (200 microg/rat, subcutaneously). Furthermore, increased gastroduodenal mucus levels were found in early-stage pregnancy rats and in animals pretreated with progesterone. These results suggest that increased progesterone plasma levels during early-stage pregnancy may be involved in pregnancy-induced gastric and duodenal protection. This effect may be related to an increase in gastric and duodenal mucus production induced by this hormone.

Animals↗
PubMed1981

Effects of cysteamine therapy in nephropathic cystinosis.

We studied the effects of cysteamine in five children with nephropathic cystinosis who were treated for up to 30 months. Cysteamine caused a decline in leukocyte cystine levels to the range seen in clinically unaffected heterozygotes; both plasma and urinary cystine diminished by more than half. Therapy had no effect on progressively declining creatinine clearance in three patients, but improvement occurred in the other two. Phosphaturia, glycosuria, aminociduria, and organic aciduria did not improve in any of the patients. Both blood lactate and the lactate pyruvate ratio were diminished. Growth velocity, which was abnormal in four of the five children, did not improve. No major side effects were noted. Therapy with cysteamine caused a consistent, dose-related decline in levels of cystine in leukocytes and in extracellular fluid, caused no improvement so far in renal tubular function or growth velocity, and improved creatinine clearance in some patients.

Amino Acids↗
PubMed1984

Radiation-induced strand breakage in poly(riboadenylic acid). A pulse radiolysis study on the protective action of cysteamine under anoxic conditions.

Poly(riboadenylic acid) was irradiated in N2O-saturated dilute aqueous solution at pH 7.8 with single pulses (50-200 ns) of 16 MeV electrons. With the aid of Rayleigh light scattering measurements both the extent and rate of main-chain scission were measured in the absence and the presence of cysteamine (RSH). In both cases two modes of light scattering intensity (LSI) decrease were detected. From this finding it was concluded that two chemically different radical sites, giving rise to main-chain breakage, were produced by OH attack on the macromolecules. Cysteamine reduced the extent of LSI decrease and accelerated the rate of the slow mode of LSI decrease significantly. The fast mode of the LSI decrease is due to fragment diffusion and therefore the influence of cysteamine on the rate of decay of the short-lived radical could not be studied. The assessment of the relative importance of .OH scavenging (RSH + .OH----RS. + H2O) and of repair (PA. + RSH----PAH + RS.) with respect to protection yielded the following: in the case of the long-lived radical, repair contributes significantly at low RSH concentration (less than 10(-4) M); in the case of the short-lived radical, OH scavenging dominates and repair becomes noticeable only at [RSH] greater than 10(-4)M. The following data were evaluated in this work: 100 eV-yield of main-chain scission, G(sb) = 1.1; lifetimes of radicals: less than 50 microseconds (short-lived), 0.6 s (long-lived), kPA. + RSH = 3.4 X 10(6)M-1 S-1 (for long-lived radicals).

Cysteamine↗
PubMed1985

Oral administration of liposome-entrapped cysteamine and the distribution pattern in blood, liver and spleen.

Oral administration of liposome-entrapped cysteamine induces an increase in the concentration of exogenous sulphur compounds in blood (plasma), liver and spleen. Among those sulphur compounds, an important amount of plasma thiols can be related to a protection of cysteamine in the digestive tract. This can account for the radioprotective effect of a liposomal-cysteamine suspension in rodents, and clearly demonstrates the interest of such a preparation in radioprotection.

Administration, Oral↗
PubMed1997

Cysteamine oxidation by lentil seedling amine oxidase.

Cysteamine is oxidatively deaminated by lentil amine oxidase. It shows saturation kinetic K(m) = 9 x 10(-4) M like other substrates, but the aldehyde produced leads to loss of enzyme activity, which is restored by dialysis. When putrescine is the substrate of the amine oxidase cysteamine behaves like a competitive inhibitor, and shows Ki = 5 x 10(-5) M. The possible involvement of the oxidation of cysteamine and the inhibitory effects of thioacetaldehyde in the cystamine oxidation by amine oxidase is discussed.

Amine Oxidase (Copper-Containing)↗
PubMedDate not supplied

In vivo cell kinetics studies of the duodenum during and after healing of cysteamine-induced duodenal ulcer in rats using bromodeoxyuridine incorporation.

The present study investigated the defect of duodenal defence responsible for the tendency of recurrence of duodenal ulcer. Male Wistar rats were treated with cysteamine-HCl subcutaneously to induce duodenal ulcer, and bromodeoxyuridine (BrdU) was given intraperitoneally 1 h before laparotomy. Serial tissue sections and immunocytochemical staining of BrdU were done to study the cell kinetics during and after healing. Deep ulcers developed in the proximal part of the duodenum 24 h after cysteamine injection, and the ulcer was replaced by scar tissue 1 week later. BrdU-labelling index of normal duodenal mucosa in control rats was 30-34%. On the peripheral part of the regenerative mucosa, BrdU-labelling index increased from 1.5% to 26-27%, 1-4 weeks after injection and remained at this level thereafter. On the central part, except the most central area, the labelling index remained at 0% until 3 weeks, and was 15% 6 weeks after cysteamine treatment. It never achieved the level seen in control normal mucosa. The labelling rate of fibrous cells in scar tissue decreased from 28% to nearly 0% 1-4 weeks after the injection. It is concluded that both the ulcer scar and the regenerative mucosa do not achieve a mature state in the initial scarred stage; they need more time to reach a relatively mature condition. Moreover, the regenerative mucosa will be the weak, easily damaged part of the duodenum.

Animals↗
PubMed1968

Cysteamine: differential x-ray protective effect on Chinese hamster cells during the cell cycle.

Cysteamine present during x-irradiation protects synchronized Chinese hamster cells in culture against lethal damage at all stages of the cell cycle. The effect is greatest for cells irradiated at sensitive stages such as G(1) and least for resistant cells; for example, late S (dose-modifying factors 4.2 and 2.7, respectively). The effect of 50 millimolar cysteamine is to render almost invariant the normally variant x-ray age response for lethality. This suggests that there are two components of x-ray damage, only one of which is age dependent, and it is against this component that cysteamine protects the cell. Cystamine, however, has no protective effect upon these cells at any stage of the cell cycle.

Animals↗
PubMed1991

Effect of nitrofurans on duodenal ulceration induced by cysteamine or indometacin.

The present experiments examined the protective effect of the nitrofuran drugs, furazolidone (FZ) and nitrofurazone (NF), on duodenal ulceration induced by cysteamine or indometacin in rats. FZ at oral doses of 25, 50 or 100 mg/kg for 2 consecutive days signficantly reduced, in a dose-dependent manner, the incidence and extent of cysteamine-induced ulceration. However, oral NF (100 mg/kg) given for 2 consecutive days had no significant effect on duodenal ulceration. The duodenal mucus content of rats was not significantly affected by either FZ or cysteamine treatments. FZ at an oral dose of 100 mg/kg for 2 consecutive days significantly reduced the incidence and extent of indometacin-induced ulceration. Smaller doses of 25 or 50 mg/kg had no significant effects.

Animals↗
PubMed2006

Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase.

There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin-induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy.

Aged↗
PubMed1992

Iron content correlates with peroxidase activity in cysteamine-induced astroglial organelles.

A subpopulation of astrocytes in periventricular brain regions and in cysteamine-treated neuroglial cultures contains cytoplasmic granules that exhibit an affinity for Gomori stains, orange-red autofluorescence, and non-enzymatic peroxidase activity. The autofluorescence and pseudoperoxidase activity are consistent with the presence of porphyrins and heme iron, respectively. In the present study, we employed diaminobenzidine cytochemistry, transmission electron microscopy, and energy-dispersive X-ray microanalysis (electron microprobe) in an attempt to correlate fine structure with the peroxidase activity and elemental composition of the cysteamine-induced inclusions in cultured astrocytes. In osmicated preparations, these membrane-bound inclusions varied greatly in size, were round or ovoid in shape, and exhibited an intensely electron-dense granular matrix. In non-osmicated preparations, many inclusions exhibited internal membranous partitions producing complex subcompartmentalization. Diaminobenzidine reaction product, indicative of endogenous peroxidase activity, was occasionally observed distributed diffusely throughout the granule matrix. More commonly, peroxidase activity was restricted to specific intraorganellar compartments. Elemental iron was detected in the inclusions by electron microprobe analysis. The presence and concentration of iron in these organelles correlated closely with the presence and intensity of diaminobenzidine staining, suggesting that redox-active iron mediates the pseudoperoxidase reactions in these cells. Cysteamine-induced derangements of porphyrin-heme biosynthesis may be responsible for the proliferation of iron-containing gliosomes in these astrocytes.

3,3'-Diaminobenzidine↗
PubMed1988

[Effect of cysteamine on vocalization responses by arterial algogenics in guinea pigs].

Effects of cysteamine (2-mercaptoethylamine) on vocalization responses, a parameter of nociceptive response, was studied in conscious guinea pigs. Intra-arterial injection of bradykinin (3 micrograms), acetylcholine (300 micrograms), capsaicin (3 micrograms) and vanillyl n-nonoylamide (3 micrograms, VNA) induced severe vocalization responses. Three hours after an administration of cysteamine (300 mg/kg, s.c.), a significant suppressive effect was observed for bradykinin and acetylcholine-evoked vocalization. A weak suppressive effect appeared in capsaicin and VNA-evoked vocalization, but there were not statistically significant changes on vocalization counts when compared with the value of the saline-treated animals. However, consecutive pretreatment of guinea pigs with VNA led to a complete suppression of capsaicinoids-evoked vocalization only. Cysteamine completely suppressed bradykinin, acetylcholine, capsaicin and VNA-evoked vocalization responses in VNA desensitized guinea pigs. These findings suggest that the mechanisms of bradykinin and acetylcholine-evoked vocalization response differ from that of capsaicinoids.

Acetylcholine↗
PubMed1989

The relationship of intraduodenal pH and delayed gastric emptying in duodenal ulceration induced by mepirizole or cysteamine in rats.

Subcutaneous administration of mepirizole (60 and 200 mg/kg) and cysteamine (100 and 300 mg/kg) to fasted rats consistently induced localized villous damage to the proximal duodenum after 6 to 8 hr. The severity of the damage in animals treated with the low doses remained unchanged at 12 hr. With the high doses, however, well-defined deep ulcers were evident by that time, the incidence being high. The agents caused a significant accumulation of highly acidic gastric contents for 6 to 8 hr, but the accumulated gastric contents had markedly decreased by 12 hr. The intraduodenal pH in these animals was significantly lowered for 8 hr with the low doses, but for 12 hr with the high doses. Both mepirizole and cysteamine significantly delayed gastric emptying which was quantitated by weighing the food residue in refed animals. This delay in emptying was observed for 6 to 8 hr with the low doses and for 12 hr with the high doses. We conclude that this prolonged accumulation of gastric contents for up to 8 hr, resulting in a continuous lowering of the intraduodenal pH for 12 hr, is a crucial factor for the progression from duodenal villous damage to visible ulcers in response to mepirizole and cysteamine.

Animals↗
PubMed1990

Possible oncostatic action of cysteamine on the pituitary glands of oestrogen-primed hyperprolactinaemic rats.

Cysteamine was investigated for its potential to reduce the size and secretion of oestrogen-primed hyperprolactinaemic rat pituitary glands. Subcutaneous administration of 80 and 120 mg cysteamine/kg significantly reduced plasma prolactin concentrations by 58 and 91% respectively, after 4h. Administration of cysteamine (60 mg s.c./kg body weight per day) for 10 days, to rats which had received an injection of 2 mg oestradiol benzoate on day 1, resulted in a significant reduction in pituitary mass (19%) and GH concentration (21%). Oral administration of 60 mg cysteamine/kg body weight to hyperprolactinaemic rats also produced a significant reduction in plasma prolactin of 94% after 2h. Oral administration of 60 mg cysteamine/kg body weight per day to rats for a 20-day period, during which they had received two injections of 2 mg oestradiol benzoate on day 1 and day 14 of treatment, resulted in a significant reduction in pituitary mass (29%) and the concentration of trunk blood prolactin concentration (35%). However, when oral cysteamine (60 mg cysteamine/kg body weight per day) was given for 20 days to rats which had been treated with 2 mg oestradiol benzoate once every 14 days over a 90-day period, it caused no change in pituitary weight, prolactin or GH concentration, or the concentration of prolactin in trunk blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗