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Title: Purification and characterization of lead-induced zinc thionein in the liver of rats

Abstract

Metallothioneins are involved in homeostasis of essential metals, but its exact biological function remains obscure. Recently it was observed that the administration of lead increased zinc content in the low molecular-weight protein fraction in the rat hepatic 105000x g soluble fraction by using Sephadex G-75 gel filtration, and that this fraction contained only zinc, not lead, as metal. Therefore, the authors have investigated the effects of some drugs on this zinc contained low molecular-weight protein (zinc binding protein, Zn-BP), and further isolated and purified the ZN-BP from liver of rats treated with lead.

Authors:
; ; ;
Publication Date:
Research Org.:
Nagasaki Univ., Japan
OSTI Identifier:
6371683
Resource Type:
Journal Article
Resource Relation:
Journal Name: Bull. Environ. Contam. Toxicol.; (United States); Journal Volume: 35:2
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; LEAD COMPOUNDS; BIOLOGICAL EFFECTS; METALLOTHIONEIN; BIOLOGICAL FUNCTIONS; CHEMICAL PREPARATION; ABSORPTION SPECTROSCOPY; ACETATES; GEL PERMEATION CHROMATOGRAPHY; LEAD CHLORIDES; LIVER; RATS; ZINC; ANIMALS; BODY; CARBOXYLIC ACID SALTS; CHLORIDES; CHLORINE COMPOUNDS; CHROMATOGRAPHY; DIGESTIVE SYSTEM; ELEMENTS; FUNCTIONS; GLANDS; HALIDES; HALOGEN COMPOUNDS; LEAD HALIDES; MAMMALS; METALLOPROTEINS; METALS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; RODENTS; SEPARATION PROCESSES; SPECTROSCOPY; SYNTHESIS; VERTEBRATES; 560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)

Citation Formats

Arizono, K., Ito, T., Ota, S., and Ariyoshi, T.. Purification and characterization of lead-induced zinc thionein in the liver of rats. United States: N. p., 1985. Web. doi:10.1007/BF01636492.
Arizono, K., Ito, T., Ota, S., & Ariyoshi, T.. Purification and characterization of lead-induced zinc thionein in the liver of rats. United States. doi:10.1007/BF01636492.
Arizono, K., Ito, T., Ota, S., and Ariyoshi, T.. Thu . "Purification and characterization of lead-induced zinc thionein in the liver of rats". United States. doi:10.1007/BF01636492.
@article{osti_6371683,
title = {Purification and characterization of lead-induced zinc thionein in the liver of rats},
author = {Arizono, K. and Ito, T. and Ota, S. and Ariyoshi, T.},
abstractNote = {Metallothioneins are involved in homeostasis of essential metals, but its exact biological function remains obscure. Recently it was observed that the administration of lead increased zinc content in the low molecular-weight protein fraction in the rat hepatic 105000x g soluble fraction by using Sephadex G-75 gel filtration, and that this fraction contained only zinc, not lead, as metal. Therefore, the authors have investigated the effects of some drugs on this zinc contained low molecular-weight protein (zinc binding protein, Zn-BP), and further isolated and purified the ZN-BP from liver of rats treated with lead.},
doi = {10.1007/BF01636492},
journal = {Bull. Environ. Contam. Toxicol.; (United States)},
number = ,
volume = 35:2,
place = {United States},
year = {Thu Aug 01 00:00:00 EDT 1985},
month = {Thu Aug 01 00:00:00 EDT 1985}
}
  • The effects of protein synthesis inhibitors, cycloheximide and puromycin, on functional thionein mRNA levels have been examined to further delineate the regulation of thionein gene expression in Cd/sup 2 +/-resistant CHO sublines proficient in Cd/sup 2 +/- or Zn/sup 2 +/-stimulated synthesis of metallothioneins. Inhibition of protein synthesis at or shortly before the time of metal-mediated induction only slightly reduces the usual increase in thionein mRNA. Protein synthesis inhibition alone does not significantly increase thionein mRNA levels. However, addition of cycloheximide 4 h after Zn/sup 2 +/ induction increases thionein mRNA activity measured 8 h after induction by at leastmore » 40%, suggesting that protein synthesis is required for normal turnover of thionein mRNA.« less
  • Kidney sulfotransferases (ST) have been shown to be involved in the biotransformation of steroid and thyroid hormones as well as xenobiotics varying from carcinogenic heterocyclic amines to drugs such as acetaminophen. In order to examine the impact of lead-induced nephrotoxicity on kidney aryl, estrogen and DHEA STs during growth and development, time-impregnated female Sprague-Dawley rats were exposed ad libitum to lead acetate (0.6%) in drinking water from gestational day 5 and continuing in male and female pups until they were sacrificed at day 85. Cytosols from male rat kidneys showed levels of estrogen ST activity (59% of females) that weremore » significantly lowered (P{le}0.05) after lead exposure (6-20% of male). Aryl ST activity was relatively unchanged in male rats after rat kidney cytosol. Immunochemical analysis of cytosols from normal males and females with the antiserums to the three STs substantiated the presence of only the aryl and estrogen STs. Immunohistochemical techniques localized the aryl and estrogen STs primarily to the S3 section of the proximal tubules. These findings indicate that kidney STs may be differently modulated during lead exposure.« less
  • (/sup 3/H)Cystine and /sup 115m/Cd were incorporated into hepatic and renal Cd-thionein in response to sc administration of 4.4 ..mu..mol of Cd/sup 2 +/ containing /sup 115m/Cd. Cd-thionein-bound /sup 115m/Cd reached a plateau by 24 and 72 h after the Cd/sup 2 +/ injection in liver and kidney, respectively. The half-life (t/sub 1/2/) of /sup 3/H-labeled hepatic Cd-thionein was 3.5 d, whereas the average t/sub 1/2/ of the soluble proteins was 3.7d. The t/sub 1/2/ of /sup 3/H-labeled renal Cd-thionein was 3.7d, whereas the average t/sub 1/2/ of the renal proteins was 3.8 d. In marked contrast, the /sup 115m/Cdmore » content of both hepatic and renal Cd-thionein was virtually unchanged, even 9 d after administration of this radionuclide. These data indicate that the protein moiety of metallothionein is degraded, although there appears to be a concomitant rebinding of Cd/sup 2 +/ to nascent thionein polypeptide chains. Thus the lack of metallothionein degradation per se does not account for the long-term retention of Cd/sup 2 +/ in liver and kdney during chronic exposure.« less
  • Circulating cadmium-thionein (Cd-MT) is cleared from the mammalian circulatory system by filtration through the kidney glomerulus with subseqent reabsorption by kidney proximal tubules. Damage to the tubules results following uptake of Cd-MT, which is dependent upon time and the dose level of cadmium administered. Intravenous administration of /sup 109/Cd-MT at doses of 0.017 and 0.17 mg Cd/kg body weight disclosed that the rate of clearance from the blood and uptake by the kidney was significantly more rapid at the 0.017 mg Cd/kg dose. Ultrastructural changes were characterized by increased numbers of pinocytotic vesicles and small, dense lysosomal structures. There wasmore » no evidence of mitochondrial swelling or cell death at either 3 or 6 h after injection. Results suggest that Cd-MT is reabsorbed and broken down by kidney tubule cells in a physiological manner with possible subsequent release of the toxic cadmium ion.« less