1.Effect of S-(1,2-dicarboxyethyl) glutathione and S-(1,2-dicarboxyethyl) cysteine on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils.
Wang C1, Lu H, Chen G, Yamashita K, Manabe M, Kodama H. Clin Chem Lab Med. 2002 Nov;40(11):1101-4.
We investigated the effects of S-(1,2-dicarboxyethyl) glutathione (DCEG) and S-(1,2-dicarboxyethyl) cysteine (DCEC) on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. When the cells were preincubated with DCEG, the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was enhanced in concentration-dependent manner but DCEC showed no effect. The influence of DCEG and DCEC on phorbol 12-myristate 13-acetate-induced superoxide generation showed no effect. On the other hand, the superoxide generation induced by arachidonic acid was markedly suppressed by DCEG and DCEC in concentration-dependent manner. The suppression of DCEG was more effective than that of DCEC. The superoxide generation induced by fMLP in the DCEG-treated cells was suppressed by genistein. DCEG enhanced tyrosyl phosphorylation of 80.0 kDa, 60.0 kDa, and 45.0 kDa proteins in human neutrophils.
2.Inhibitory effects of S-(1,2-dicarboxyethyl)glutathione on collagen-induced platelet aggregation; enhancements of cyclic AMP level and adenylate cyclase activity in platelets by S-(1,2-dicarboxyethyl)glutathione.
Tsuboi S1, Fujiwara E, Ogata K, Sakaue A, Nakayama T, Ohmori S. Biol Pharm Bull. 1993 Nov;16(11):1083-6.
S-(1,2-Dicarboxyethyl)glutathione (DCE-GS) in addition to being present in the liver, lens, and heart, also inhibited platelet aggregation. To clarify these inhibitory effects, the role of DCE-GS in the release of ATP and serotonin from platelets was studied, as was thromoboxane A2 formation, cyclic AMP level and adenylate cyclase activity in human platelets. The results are as follows: DCE-GS at a concentration of 1.3 mM inhibited ATP and serotonin release from platelets induced by collagen, by 77.4 +/- 4.3 and 78.7 +/- 6.3%, respectively. At 1.5 mM DCE-GS also inhibited the formation of thromboxane B2 by 79.6 +/- 4.1%. Incubation of human platelet rich plasma with 2 mM of DCE-GS for 10 min increased the cyclic AMP level and the activity of adenylate cyclase by 204 +/- 28 and 211 +/- 11.7%, respectively. These results suggest that the inhibitory effect of DCE-GS on the platelet aggregation induced by collagen is due to an increase in the cyclic AMP level in platelets, which in turn may be due to enhancement of the activity of adenylate cyclase.
3.S-(1,2- dicarboxyethyl)glutathione and glutathione in lens and liver of napthalene-treated rabbits.
Takemura M1, Ueno H, Kodama H. Eur J Clin Chem Clin Biochem. 1996 Feb;34(2):85-90.
The determination of S-(1,2-dicarboxyethyl)glutathione and reduced glutathione (GSH) in the rabbit lens and liver was developed using an isotachophoretic analyser. The recovery of S-(1, 2-dicarboxyethyl)GSH from the rabbit liver after ion-exchange treatment was 96.8 +/- 11.3% (n=3). The contents of S-(1,2-dicarboxyethyl)GSH in the rabbit lens and liver were 219.9 +/- 29.1 (n=5) and 44.0 +/- 13.5 (n = 8) nmol/g, respectively. The contents of S-(1, 2-dicarboxyethyl)GSH in the lens and GSH in the lens and liver of naphthalene-treated rabbits was also determined by this method 24 hours after naphthalene administration, at which time the axial opacity "spichen" was observed at the equatorial region of the lens. The content of S-(1,2-dicarboxyethyl)GSH in the lens decreased in proportion to the content of GSH. During the further development of true lens opacity after naphthalene administration, the S-(l, 2-dicarboxyethyl)GSH content further compared with that in the spichen stage, but the S-(1, 2-dicarboxyethyl)GSH content of the lens that did not develop true opacity after naphthalene administration returned to the normal level.
4.Structure of a glutathione conjugate bound to the active site of aldose reductase.
Singh R1, White MA, Ramana KV, Petrash JM, Watowich SJ, Bhatnagar A, Srivastava SK. Proteins. 2006 Jul 1;64(1):101-10.
Aldose reductase (AR) is a monomeric NADPH-dependent oxidoreductase that catalyzes the reduction of aldehydes, ketones, and aldo-sugars. AR has been linked to the development of hyperglycemic injury and is a clinical target for the treatment of secondary diabetic complications. In addition to reducing glucose, AR is key regulator of cell signaling through it's reduction of aldehydes derived from lipoproteins and membrane phospholipids. AR catalyzes the reduction of glutathione conjugates of unsaturated aldehydes with higher catalytic efficiency than free aldehydes. The X-ray structure of human AR holoenzyme in complex with the glutathione analogue S-(1,2-dicarboxyethyl) glutathione (DCEG) was determined at a resolution of 1.94 A. The distal carboxylate group of DCEG's dicarboxyethyl moiety interacted with the conserved AR anion binding site residues Tyr48, His110, and Trp111. The bound DCEG's glutathione backbone adopted the low-energy Y-shape form.
