diethyl-maleate and sodium-arsenite

Exposure of mouse peritoneal macrophages to oxidative and sulfhydryl-reactive agents in vitro enhances synthesis of a few cellular proteins that may be important in a self-defense system. A cDNA encoding a novel stress-inducible protein, designated MSP23 (macrophage 23-kDa stress protein), was cloned from a cDNA library of the macrophages by differential screening. A 1.0-kilobase mRNA transcript hybridized with the MSP23 cDNA gradually increased in macrophages upon culture in vitro. Treatment with diethylmaleate or glucose/glucose oxidase, which generates H2O2, markedly enhanced the induction of the transcript after several hours. Cadmium chloride and sodium arsenite also induced the transcript. An antiserum raised against recombinant MSP23 reacted with the 23-kDa stress-inducible protein of the macrophages. The amounts of 23-kDa protein in the cells rapidly increased during culture with diethylmaleate. The mRNA was detected in various tissues, and it was especially high in content in the liver. A search of databases revealed that six proteins of various species from bacteria to the mouse have a sequence homology to MSP23. One of the proteins is the C22 component of alkyl hydroperoxide reductase, which is induced by hydrogen peroxide in Salmonella typhimurium.

Topics: Amino Acid Sequence; Animals; Arsenic; Arsenites; Base Sequence; Blotting, Northern; Cells, Cultured; Cloning, Molecular; DNA; Heat-Shock Proteins; Hydrogen Peroxide; Immunoblotting; Immunosorbent Techniques; Macrophages; Maleates; Mice; Molecular Sequence Data; Molecular Weight; Nucleic Acid Hybridization; Peritoneal Cavity; Peroxidases; Peroxiredoxins; Protein Biosynthesis; RNA, Messenger; Sodium Compounds; Tissue Distribution

This study aimed to clarify whether glutathione (GSH) plays a role in the hepatobiliary transport of arsenic. For this purpose, the biliary excretion of 74As was measured in urethane-anaesthetized rats for 2 hr after the administration of labelled sodium arsenite (50 mumol/kg, i.v.) or arsenate (150 mumol/kg, i.v.) and under the influence of sulfobromophthalein (BSP), indocyanine green (ICG) or diethyl maleate (DEM) which are known to diminish hepatobiliary transport of GSH. Although the biliary excretion of arsenic was different after arsenite and arsenate administration in terms of quantity (19% vs 6% of dose in 2 hr, respectively) and time course, arsenic excretion responded similarly to BSP (50 mumol/kg, i.v.), ICG (25 mumol/kg, i.v.) or DEM (4 mumol/kg, i.p.) irrespective of the injected arsenical. Initially the biliary excretion of arsenic in rats with either arsenite or arsenate was significantly reduced, but then moderately increased by BSP and, more lastingly, depressed by ICG, whereas it was virtually abolished by DEM. The responses of arsenic excretion to BSP, ICG and DEM were related, both proportionally and temporally, to the effects exerted by these agents on the hepatobiliary transport of GSH, as assessed by the biliary excretion of non-protein thiols. These findings indicate that the biliary excretion of arsenic after the administration of either arsenite or arsenate is dependent on the hepatobiliary transport of GSH. Transport of arsenic as a GSH complex may account for the GSH dependence of biliary arsenic excretion.

Topics: Animals; Arsenates; Arsenic; Arsenites; Bile; Biological Transport; Female; Glutathione; Indocyanine Green; Liver; Maleates; Rats; Rats, Inbred Strains; Sodium Compounds; Sulfhydryl Compounds; Sulfobromophthalein