S-Methylthio-Cysteine and Cystamine Are Potent Stimulators of Thiol Production and Glutathione Synthesis

Jókay, István; Kelemenics, K.; Gyuris, Ágnes; Minárovits, János

doi:10.1016/s0024-3205(97)01066-7

Cited by 21 publications

(13 citation statements)

References 25 publications

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“…This was attributed to thiol-disulfide exchange reactions with cystine, which could either release cysteine or increase uptake of cystine[21,22,23]. Free cysteine could interact with free cysteamine, be oxidised to cystine or enter the glutathione pool[20].…”

Section: Biochemistry Of Vaninmentioning

confidence: 99%

Diverse biological activities of the vascular non-inflammatory molecules – The Vanin pantetheinases

Kaskow

Proffit

Blangero

et al. 2012

Biochemical and Biophysical Research Communications

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The Vanin genes are a family that encode pantetheinases involved in recycling Coenzyme A, caytalysing the breakdown of intermediate panetheine to vitamin B5 for reuse in CoA biosynthesis. The role of pantetheinase in this most fundamental of cellular processes, was substantially characterised by the 1970s. The next 20 years saw little further interest in pantetheinase until various genetic studies implicated the vanin locus in a range of normal and disease phenotypes, and a consequent interest in the other product of pantetheinase activity, cysteamine. This report seeks to bring together the early biochemical studies with recent biological data implicating cysteamine as a regulator of the oxidative state of a cell. Numerous studies now report a role for Vanin in inflammation, oxidative stress, cell migration and numerous diseases including cardiovascular disease.

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Section: Biochemistry Of Vaninmentioning

confidence: 99%

Diverse biological activities of the vascular non-inflammatory molecules – The Vanin pantetheinases

Kaskow

Proffit

Blangero

et al. 2012

Biochemical and Biophysical Research Communications

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“…28 CysN is able to reduce apoptotic processes by the inhibition of the thiol-dependent protease caspase 3, a pivotal downstream enzyme in the programmed cell death, 7 and to ameliorate redox balance through the increase of the intracellular glutathione levels with a consequent increase of the reductive power. 29 However, caspase inhibition has been demonstrated only in vitro, 7 and increase of glutathione levels could be modest. 30,31 Besides these effects, CysN is also a relevant inhibitor of the TGs and in particular of TG2, the most-studied enzyme.…”

Section: Cystamine Reduces Inflammation L Elli Et Almentioning

confidence: 99%

Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease

Elli

Ciulla

Busca

et al. 2011

Laboratory Investigation

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Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n ¼ 7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n ¼ 8); treated with TNBS enema plus oral CysN (TNBS-CysN group; n ¼ 8); treated with CysN (CysN group; n ¼ 7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-a (TNF-a) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS-CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43 ± 0.78 vs 3.28 ± 0.95, microscopic score 6.62 ± 12.01 vs 19.25 ± 6.04, Po0.05, respectively) associated with a decrease of TG activity, TG2 and isopeptide bond immunohistochemical expression, TNF-a and IL-6 levels. No statistically significant differences were found between CysN and CTR groups. The colonic immunolocalization of TG2 was comparable in humans affected by IBD and TNBS-administered animals. This is the first demonstration that treatment with a CysN has an anti-inflammatory effect, reducing severity of colitis in a rat model. CysN could be tested as a possible treatment or co-treatment in IBD therapeutic trials.

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“…Treatment with Cystamine Results in an Increase in Glutathione Level-Because it has been previously suggested that cystamine treatment may affect the state of the glutathione system (30,31), the effects of cystamine on the level of glutathione in the cell were examined. SH-SY5Y cells were incubated in the absence or presence of 250 M cystamine for 8 h prior to collection and measurement of the levels of glutathione (GSH ϩ GSSG) (Fig.…”

Section: Figmentioning

confidence: 99%

Cystamine Inhibits Caspase Activity

Lesort

Lee

Tucholski

et al. 2003

Journal of Biological Chemistry

157

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Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormally expended polyglutamine domain. There is no effective treatment for HD; however, inhibition of caspase activity or prevention of mitochondria dysfunction delays disease progression in HD mouse models. Similarly administration of cystamine, which can inhibit transglutaminase, prolonged survival of HD mice, suggesting that inhibition of transglutaminase might provide a new treatment strategy. However, it has been suggested that cystamine may inhibit other thiol-dependent enzymes in addition to transglutaminase. In this study we show that cystamine inhibits recombinant active caspase-3 in a concentration-dependent manner. At low concentrations cystamine is an uncompetitive inhibitor of caspase-3 activity, becoming a non-competitive inhibitor at higher concentrations. The IC 50 for cystaminemediated inhibition of caspase-3 activity in vitro was 23.6 M. In situ cystamine inhibited in a concentrationdependent manner the activation of caspase-3 by different pro-apoptotic agents. Additionally, cystamine inhibited caspase-3 activity to the same extent in cell lines stably overexpressing wild type tissue transglutaminase (tTG), a mutant inactive tTG, or an antisense for tTG, demonstrating that cystamine inhibits caspase activity independently of any effects it may have on the transamidating activity of tTG. Finally, treatment with cystamine resulted in a robust increase in the levels of glutathione. These findings demonstrate that cystamine may prolong neuronal survival and delay the onset of HD by inhibiting caspases and increasing the level of antioxidants such as glutathione.

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S-Methylthio-Cysteine and Cystamine Are Potent Stimulators of Thiol Production and Glutathione Synthesis

Cited by 21 publications

References 25 publications

Diverse biological activities of the vascular non-inflammatory molecules – The Vanin pantetheinases

Diverse biological activities of the vascular non-inflammatory molecules – The Vanin pantetheinases

Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease

Cystamine Inhibits Caspase Activity

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