Disease relevance of DCVC

• Aminoxyacetic acid blocks both the metabolism of S-(1,2-dichlorovinyl)-L-cysteine to a reactive species which covalently binds to cellular macromolecules and toxicity [1].
• Chronic exposure to low concentrations of the nephrotoxic cysteine conjugate S-(1,2-dichlorovinyl)-l-cysteine (DCVC) causes cataracts in mice [2].
• Colchicine antimitosis causes progression of S-(1,2-dichlorovinyl)-L-cysteine-induced injury leading to acute renal failure and death in mice [3].
• S-(1,2-dichlorovinyl)-L-cysteine-induced nephrotoxicity in the New Zealand white rabbit: characterization of proteinuria and examination of the potential role of oxidative injury [4].

High impact information on DCVC

• In quiescent LLC-PK1 renal epithelial cells, c-myc but not max or mad mRNA is induced by the nephrotoxicant S-(1,2-dichlorovinyl)-L-cysteine (DCVC) [5].
• The purified mitochondrial enzyme is similar to the cytosolic glutamine transaminase K whose beta-lyase activity with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) is regulated by concurrent transamination (Stevens, J. L., Robbins, J. D., and Byrd, R. A. (1986) J. Biol. Chem. 261, 15529-15537) [6].
• LLC-PK1 cells have the degradative enzymes of the mercapturate pathway, and S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)-L-glutathione are toxic [1].
• The role of complex II in the cellular protection against oxidative stress was investigated in freshly isolated rat renal proximal tubular cells (PTC) with the use of the nephrotoxin S-(1,2-dichlorovinyl)-L-cysteine (DCVC) [7].
• Therefore, we have investigated the polarity and the molecular driving forces for the transport of S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in isolated membrane vesicles from rat kidney cortex [8].

Chemical compound and disease context of DCVC

• Mechanism of S-(1,2-dichlorovinyl)-L-cysteine- and S-(1,2-dichlorovinyl)-L-homocysteine-induced renal mitochondrial toxicity [9].
• This article focuses on the various models for kidney toxicity due to trichloroethylene (TCE) and its glutathione-dependent metabolites, in particular S-(1,2-dichlorovinyl)-l-cysteine [10].
• N-acetyl S-(1,2-dichlorovinyl)-L-cysteine produces a similar toxicity to S-(1,2-dichlorovinyl)-L-cysteine in rabbit renal slices: differential transport and metabolism [11].

Biological context of DCVC

• Exposure of primary cultures of RPTC to the nephrotoxic cysteine conjugate, S-(1,2-dichlorovinyl)-l-cysteine (DCVC), resulted in 9% apoptosis and 30% necrosis at 24 h following the exposure [12].
• Protein kinase C-alpha inhibits the repair of oxidative phosphorylation after S-(1,2-dichlorovinyl)-L-cysteine injury in renal cells [13].
• Previous studies showed that S-(1,2-dichlorovinyl)-L-cysteine perturbs intracellular Ca2+ homeostasis [Vamvakas et al., Mol Pharmacol 38: 455-461, 1990] [14].
• Apoptosis, necrosis, and cell proliferation induced by S-(1,2-dichlorovinyl)-L-cysteine in primary cultures of human proximal tubular cells [15].
• Changes in gene expression in human renal proximal tubule cells exposed to low concentrations of S-(1,2-dichlorovinyl)-l-cysteine, a metabolite of trichloroethylene [16].

Anatomical context of DCVC

• Nephrotoxic cysteine S-conjugates of halogenated hydrocarbons that require bioactivation by cysteine conjugate beta-lyase (S-(1,2-dichlorovinyl)-L-cysteine (DCVC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine, CTFC) were potent inhibitors of state 3 respiration in rat kidney mitochondria [17].
• The transport of S-cysteine conjugates was studied in the kidney cell line, LLC-PK1, using the nephrotoxin, S-(1,2-dichlorovinyl)-L-cysteine (L-DCVC), as the model compound [18].
• Na-dependent transport of S-(1,2-dichlorovinyl)-L-cysteine by renal brush-border membrane vesicles [19].
• Effects of S-(1,2-dichlorovinyl)-L-cysteine on the transport of para-aminohippurate ion in renal plasma membrane vesicles [20].

Associations of DCVC with other chemical compounds

• We obtained highly purified mitochondrial glutamine transaminase K and showed that it possesses little cysteine S-conjugate beta-lysae activity with S-(1,2-dichlorovinyl)-L-cysteine and S-(1,1,2,2-tetrafluoroethyl)-L-cysteine as substrates [21].
• NRK-52E cells were stably transfected with the cDNA for WT-rOGC and exhibited 10- to 20-fold higher GSH transport activity than nontransfected cells and were markedly protected from apoptosis induced by tert-butyl hydroperoxide (tBH) or S-(1,2-dichlorovinyl)-L-cysteine (DCVC) [22].
• Roles of cysteine conjugate beta-lyase and S-oxidase in nephrotoxicity: studies with S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)-L-cysteine sulfoxide [23].
• The nephrotoxicant S-(1,2-dichlorovinyl)-L-cysteine (DCVC) is an alkylating agent that causes oxidative stress and subsequently death of renal proximal tubular cells (PTC) [24].
• Cysteine S-conjugate beta-lyase activity is detected in the gel by incubating the gel with a reaction mixture containing alpha KMB (to ensure maintenance of the enzyme in the pyridoxal 5'-phosphate form), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), PMS, and NBT [25].

Gene context of DCVC

• Results also show that FMO3 orthologs from multiple species are catalytically similar with regard to methionine, S-allyl-L-cysteine, and S-(1,2-dichlorovinyl)-L-cysteine S-oxidations [26].
• In this study we investigated by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis and direct sequencing if S-(1,2-dichlorovinyl)-L-cysteine-induced LLC-PK1 clones display mutations in the p53 gene in comparison with wild-type clones [27].
• We now show that S-(1,2-dichlorovinyl)-L-cysteine and another nephrotoxic cysteine S-conjugate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, inactive purified cytosolic aspartate aminotransferase and purified alanine aminotransferase [28].
• Depletion of cytochrome P-450 and alterations in activities of drug metabolizing enzymes by S-(1,2-dichlorovinyl)-L-cysteine in mouse kidney cortex [29].

References