Cystamine 2HCl can inhibit transglutaminase and interrupt with sulfhydryl enzymes. It is used as a radiation-protective agent, eparin antagonist and thiol modification reagent.
TG2 (transglutaminase 2) mediates covalent cross‐links of structural proteins, acts as a G-protein (Gh) in transmembrane signalling and is involved in cell proliferation, cell adhesion, apoptosis, cell–matrix interactions and reorganization of extracellular matrix. Cystamine have been shown to be neuroprotective, to increase survival, to improve motor performance in Huntington's disease and to reduce neuronal loss in animal models of Parkinson's disease. The therapeutic benefits mediated by cystamine have, in part, been attributed to inhibition of TG2[1]. Cystamine concentration-dependently inhibited responses to phenylephrine, 5-HT and U46619 and for extracellular potassium. Cystamine relaxed and reduced [Ca2+]i in phenylephrine-contracted arteries. In potassium-contracted arteries, cystamine induced less relaxation without changing [Ca2+]i, and these relaxations were blocked by mitochondrial complex inhibitors. Cystamine induced vasodilatation by inhibition of receptor-coupled TG2, leading to opening of Kv channels and reduction of intracellular calcium, and by activation of a pathway sensitive to inhibitors of the mitochondrial complexes I and III. Both pathways may contribute to the antihypertensive and neuroprotective effect of cystamine[1]. Cystamine has been shown to cause marked suppression of HIV replication in cultured lymphocytes and macrophages[2]. CD studies showed the interesting ability of cystamine to shift the equilibrium B/A-DNA towards the B-form[3]. In vivo, treatment of chronically infected macrophages with cystamine, at a concentration (500 µM) that did not show any cytotoxic or cytostatic effects, strongly decreased (> 80%) HIV-p24 antigen production and completely abolished the production of infectious viral particles[4].
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