Biliary transport of glutathione S-conjugate by rat liver canalicular membrane vesicles.

Inoue, Masayasu; Akerboom, Theodorus P.M.; Sies, Helmut; Kinne, Rolf; Thao, Tran Xuan; Arias, Irwin M.

doi:10.1016/s0021-9258(17)42945-0

Cited by 102 publications

(1 citation statement)

References 33 publications

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“…The presence of SCEG, which is presumably formed intracellularly, in the medium may be explained by lysis of damaged cells and release of SCEG into the medium or by active transport of the conjugate from viable cells. Rat liver canalicular membrane vesicles (Inoue et al, 1984) and rat hepatocyte plasma membrane fractions (Nicotera et al, 1985) both contain transport systems that may function in the cellular extrusion of glutathione S conjugates.…”

Section: Discussionmentioning

confidence: 99%

Role for an episulfonium ion in S-(2-chloroethyl)-DL-cysteine-induced cytotoxicity and its reaction with glutathione

Webb¹,

Elfarra²,

Webster³

et al. 1987

Biochemistry

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The cysteine S conjugate of 1,2-dichloroethane, S-(2-chloroethyl)-DL-cysteine (CEC), is hepatotoxic, nephrotoxic, and mutagenic. To determine the cellular and chemical mechanisms involved in CEC-induced toxicity and to assess the role of an episulfonium ion, the effect of CEC on the viability of isolated rat hepatocytes was studied. CEC addition resulted in both a time- and concentration-dependent loss of cell viability. Depletion of intracellular glutathione concentrations (greater than 70%) and inhibition of microsomal Ca2+ transport and Ca2+-ATPase activity preceded the loss of cell viability, and initiation of lipid peroxidation paralleled the loss of viability. The depletion of glutathione concentrations was partially attributable to a reaction between glutathione and CEC to form S-[2-(DL-cysteinyl)ethyl]glutathione, which was identified by NMR and mass spectrometry. N-Acetyl-L-cysteine, vitamin E, and N,N'-diphenyl-p-phenylenediamine protected against the loss of cell viability. N,N'-Diphenyl-p-phenylenediamine inhibited CEC-initiated lipid peroxidation but did not protect against cell death at 4 h, indicating that lipid peroxidation was not the cause of cell death. The analogues S-ethyl-L-cysteine, S-(3-chloropropyl)-DL-cysteine, and S-(2-hydroxyethyl)-L-cysteine, which cannot form an episulfonium ion, were not cytotoxic, thus demonstrating a role for an episulfonium ion in the cytotoxicity associated with exposure to CEC and, possibly, 1,2-dichloroethane. These results show that an alteration in Ca2+ homeostasis and the generation of an electrophilic intermediate may be involved in the mechanism of cell death.

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Section: Discussionmentioning

confidence: 99%

Role for an episulfonium ion in S-(2-chloroethyl)-DL-cysteine-induced cytotoxicity and its reaction with glutathione

Webb¹,

Elfarra²,

Webster³

et al. 1987

Biochemistry

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Formation of activated oxygen in the hypoxic rat liver

Räder

Siems

Müller

et al. 1985

Cell Biochemistry & Function

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The biliary GSSG efflux rate of normoxic perfused rat liver was 1.5 +/- 0.2 nmol/min/g liver wet weight. The GSSG efflux rate as indicator for the flux through the glutathione peroxidase reaction and, therefore, for an oxidative loading increased with the extent of hypoxia. 2.6 +/- 0.5 nmol/min/g were released from the severely hypoxic liver. The hydroxyl radical scavenger formate as well as the xanthine oxidase inhibitor allopurinol reduced the efflux rate of GSSG. GSH was released from the perfused liver at a rate of 15.5 nmol/min/g which was nearly unchanged in severe hypoxia. The high rate of glucose liberation from the hypoxic liver declined to almost that of the normoxic organ in the presence of formate. There is an 'oxidative stress' during hypoxic liver perfusion which probably originates from increased generation of activated oxygen species in the degradation of purine nucleotides.

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Special article the glutathione S-transferases: An update

Boyer

1989

Hepatology

208

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Over the last 15 years, we have passed through an initial period in which multiple forms of GST in various organs and different species were identified and characterized. The focus of current research is to define the role of the numerous isozymes in cell function, to ascertain the relationship between structure and function of different isozymes and to determine how the expression of GST is regulated in different tissues. During these studies, it is expected that new roles for the GST will be proposed, and this family of multifunctional proteins will continue to hold the interest of numerous investigators for many years.

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Biliary transport of glutathione S-conjugate by rat liver canalicular membrane vesicles.

Cited by 102 publications

References 33 publications

Role for an episulfonium ion in S-(2-chloroethyl)-DL-cysteine-induced cytotoxicity and its reaction with glutathione

Role for an episulfonium ion in S-(2-chloroethyl)-DL-cysteine-induced cytotoxicity and its reaction with glutathione

Formation of activated oxygen in the hypoxic rat liver

Special article the glutathione S-transferases: An update

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