Metallothionein and cellular protection

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Project Title: Metallothionein and cellular protection
Principal Investigators (PI): RICHARDSON ARLAN G
Project Number: 1R01ES006277-01
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
 
Project Description:
The metallothioneins (MTs) are a group of small, ubiquitous, cysteine- rich proteins that avidly bind heavy metal ions. Because MT binds to and is induced by heavy metal ions, it is generally believed that MT evolved to protect living organisms against the toxicity of heavy metals. However, investigators have argued persuasively that it is unlikely that the primary function of MT is to protect cells against heavy metals. Thus the exact function of MT remains an enigma. Gene transfer studies with mammalian cell lines demonstrate that the over-expression of MT results in the cells becoming resistant to the toxicity of heavy metals and alkylating agents. The latter observation is of interest because alkylating agents are known to be carcinogenic in mammals. Although some correlative data suggests that increased levels of MT also protect tissues in vivo against the toxicity of heavy metals, this association is not always observed. At the present time, there is not information about the potential role MT might play in protecting tissues against the toxic and carcinogenic action of alkylating agents. The objective of this project is to produce transgenic mice that over- express MT and to use these mice to test the following hypothesis: Increased expression of MT will protect an organism from the cytotoxic and carcinogenic action of heavy metals and alkylating agents. The specific aims of this project are as follows: 1. To produce and characterize transgenic mice that carry the human- transferrin promoter fused to the human MT-II(Alpha) gene (phTF/hMT- II(alpha). These transgenic mice will over-express the MT-II(Alpha) gene in liver and brain. 2. To determine if the over-expression of MT protects an organism from the toxicity of heavy metals. The hepatotoxicity of Cd will be compared in phTF/hMT-II(Alpha) transgenic mice and mice without the transgene, and the mechanism responsible for the reduced hepatotoxicity will be studied. 3. To determine if the over-expression of MT protects an organism from carcinogenesis induced by alkylating agents. The ability of N-nitroso-N- methylurea(NMU) to induce liver tumors in phTF/hMT-II(Alpha) transgenic mice and mice without the transgene will be compared, and the mechanism responsible for the reduced hepatocarcinogenesis will be studied.
 
Project Terms:
methylnitrosourea chemical carcinogenesis liver neoplasms metal poisoning cadmium metallothionein gene expression cytotoxicity transferrin hepatotoxin fusion gene brain metabolism genetic promoter element glutathione genetically modified animals laboratory mouse
Project Title: Metallothionein and cellular protection
Principal Investigators (PI): RICHARDSON ARLAN G
Project Number: 1R01ES006277-01
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
 
Project Categories:
• Natural Sciences > Aging Diseases and Pathology > Cardiovascular and cerebrovascular diseases > Cardiomyopathy
 
Other Information:
Fiscal Year: 1993
Project Start Date: 1 January 1992
Project End Date: 31 December 1995
Administering Institute Or Center: NIEHS
 
Project Funding Information:
Total Funding: $136,913
Year Funding Organization Total Funding, $
1993 NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES $136,913
Project Title: Metallothionein and cellular protection
Principal Investigators (PI): RICHARDSON ARLAN G
Project Number: 1R01ES006277-01
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
 
Project_number Title Year FY Total Cost
There are no results for this project in database.
Project Title: Metallothionein and cellular protection
Principal Investigators (PI): RICHARDSON ARLAN G
Project Number: 1R01ES006277-01
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
 
Project number Project title Organization FY Funding Organization FY Total Cost
5R01AG001548-09EFFECT OF DIETARY RESTRICTION ON GENE EXPRESSIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1992NATIONAL INSTITUTE ON AGING
$192,072
5R01AG001548-10EFFECT OF DIETARY RESTRICTION ON GENE EXPRESSIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1993NATIONAL INSTITUTE ON AGING
$199,283
1T35AG000230-01SHORT-TERM TRAINING FOR MINORITY STUDENTSUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1993NATIONAL INSTITUTE ON AGING
$46,332
1R01ES006277-01METALLOTHIONEIN AND CELLULAR PROTECTIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1993NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
$136,913
5R01AG001548-11DIETARY RESTRICTION EFFECT ON GENE EXPRESSIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1994NATIONAL INSTITUTE ON AGING
$211,996
5T35AG000230-02SHORT-TERM TRAINING STUDENTS IN HLTH PROF SCHOOLSUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1994NATIONAL INSTITUTE ON AGING
$51,786
5R01ES006277-02METALLOTHIONEIN AND CELLULAR PROTECTIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1994NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
$142,389
1P30AG013319-01NATHAN SHOCK AGING CENTERUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1995NATIONAL INSTITUTE ON AGING
$417,765
5T35AG000230-03SHORT-TERM TRAINING STUDENTS IN HLTH PROF SCHOOLSUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1995NATIONAL INSTITUTE ON AGING
$51,786
2R01AG001548-12DIETARY RESTRICTION EFFECT ON GENE EXPRESSIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1995NATIONAL INSTITUTE ON AGING
$172,765
5R01ES006277-03ROLE OF METALLOTHIONEIN IN CELLULAR PROTECTIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1995NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
$160,243
5P30AG013319-02NATHAN SHOCK AGING CENTERUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1996NATIONAL INSTITUTE ON AGING
$479,058
5R01AG001548-13EFFECT OF DIETARY RESTRICTION ON GENE EXPRESSIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1996NATIONAL INSTITUTE ON AGING
$174,065
2T35AG000230-04SHORT-TERM TRAINING STUDENTS IN HEALTH PROFESSIONAL SCHOUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1996NATIONAL INSTITUTE ON AGING
$52,056
5T35AG000230-05SHORT-TERM TRAINING STUDENTS IN HEALTH PROFESSIONAL SCHOUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1997NATIONAL INSTITUTE ON AGING
$52,056
3P30AG013319-02S1NATHAN SHOCK AGING CENTERUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1997NATIONAL INSTITUTE ON AGING
$45,000
5R01AG001548-14EFFECT OF DIETARY RESTRICTION ON GENE EXPRESSIONUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1997NATIONAL INSTITUTE ON AGING
$180,095
5P30AG013319-03NATHAN SHOCK AGING CENTERUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1997NATIONAL INSTITUTE ON AGING
$499,173
1R01AG015134-01TRANSGENIC MODELS TESTING ROLE OF DNA DAMAGE IN AGINGUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1997NATIONAL INSTITUTE ON AGING
$350,154
5P01AG014674-02NUTRITIONAL PROBE OF THE AGING PROCESSUNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT1999NATIONAL INSTITUTE ON AGING
$1,131,504
Project Title: Metallothionein and cellular protection
Principal Investigators (PI): RICHARDSON ARLAN G
Project Number: 1R01ES006277-01
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
 
Project number Project title Principal investigator
There are no any related projects.
Project Title: Metallothionein and cellular protection
Principal Investigators (PI): RICHARDSON ARLAN G
Project Number: 1R01ES006277-01
Organization: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
 
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