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Title: Metallothionein turnover in mammalian cell lines: implications in drug resistance

Abstract

Metallothioneins (MT) are low molecular weight, cysteine-rich proteins believed to participate in metal detoxification. A wide variety of cells in culture have been shown to accumulate MT in response to metal administration. These metal-induced increases in MT levels result from an increased rate of MT gene transcription, MT mRNA accumulation, and MT synthesis. Turnover of Cd-, Zn- and Au-induced MT was studied in a Chinese Hamster Ovary (CHO) cell line which was resistant to Cd and the Au-containing drug Auranofin (AF). Cd, Zn and Au were potent inducers of MT mRNA and accumulated approximately equal amounts of mRNA under the conditions employed in this study. Pulse-chase studies utilizing (/sup 35/S)cysteine revealed that the half-life of Au-, Zn- and Cd-induced MT was 0.75, 10 and 24 hrs. respectively. The reported differences in the tertiary structure of Au-MT from that of Cd-MT lead us to propose that the differences in half-lives observed reflect differences in subceptibility to intracellular proteolysis, which in turn, may effect the ability of MT to confer resistance to various metals.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Smith Kline and French Labs., Philadelphia, PA
OSTI Identifier:
5202646
Alternate Identifier(s):
OSTI ID: 5202646
Report Number(s):
CONF-8606151-
Journal ID: CODEN: FEPRA
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; CADMIUM; BIOLOGICAL EFFECTS; CHO CELLS; SENSITIVITY; GOLD; METALLOTHIONEIN; BIOSYNTHESIS; ZINC; BIOLOGICAL HALF-LIFE; CELL CULTURES; CYSTEINE; GENES; MESSENGER-RNA; SULFUR 35; TRACER TECHNIQUES; TRANSCRIPTION; AMINO ACIDS; ANIMAL CELLS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; CARBOXYLIC ACIDS; DAYS LIVING RADIOISOTOPES; ELEMENTS; EVEN-ODD NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; METALLOPROTEINS; METALS; NUCLEI; NUCLEIC ACIDS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PROTEINS; RADIOISOTOPES; RNA; SULFUR ISOTOPES; SYNTHESIS; THIOLS; TRANSITION ELEMENTS 560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987); 550201 -- Biochemistry-- Tracer Techniques

Citation Formats

Monia, B.P., Butt, T.R., Ecker, D.J., Mirabelli, C.K., and Crooke, S.T. Metallothionein turnover in mammalian cell lines: implications in drug resistance. United States: N. p., 1986. Web.
Monia, B.P., Butt, T.R., Ecker, D.J., Mirabelli, C.K., & Crooke, S.T. Metallothionein turnover in mammalian cell lines: implications in drug resistance. United States.
Monia, B.P., Butt, T.R., Ecker, D.J., Mirabelli, C.K., and Crooke, S.T. Thu . "Metallothionein turnover in mammalian cell lines: implications in drug resistance". United States.
@article{osti_5202646,
title = {Metallothionein turnover in mammalian cell lines: implications in drug resistance},
author = {Monia, B.P. and Butt, T.R. and Ecker, D.J. and Mirabelli, C.K. and Crooke, S.T.},
abstractNote = {Metallothioneins (MT) are low molecular weight, cysteine-rich proteins believed to participate in metal detoxification. A wide variety of cells in culture have been shown to accumulate MT in response to metal administration. These metal-induced increases in MT levels result from an increased rate of MT gene transcription, MT mRNA accumulation, and MT synthesis. Turnover of Cd-, Zn- and Au-induced MT was studied in a Chinese Hamster Ovary (CHO) cell line which was resistant to Cd and the Au-containing drug Auranofin (AF). Cd, Zn and Au were potent inducers of MT mRNA and accumulated approximately equal amounts of mRNA under the conditions employed in this study. Pulse-chase studies utilizing (/sup 35/S)cysteine revealed that the half-life of Au-, Zn- and Cd-induced MT was 0.75, 10 and 24 hrs. respectively. The reported differences in the tertiary structure of Au-MT from that of Cd-MT lead us to propose that the differences in half-lives observed reflect differences in subceptibility to intracellular proteolysis, which in turn, may effect the ability of MT to confer resistance to various metals.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:6,
place = {United States},
year = {Thu May 01 00:00:00 EDT 1986},
month = {Thu May 01 00:00:00 EDT 1986}
}

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