Document Detail


Thyroid hormone responsive protein (THRP) mediates thyroid hormone-induced cytotoxicity in primary neuronal cultures.
MedLine Citation:
PMID:  15490139     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The thyroid hormone responsive protein (THRP) is a novel gene product that remains responsive to thyroid hormone (TH) in the cerebral cortex of adult rats. To study the effects of THRP on neuronal cell survival, primary neurons cultured from rats at embryonic day 19 were treated with either 10(-7) mol L(-1) 3,5,3'-triiodothyronine (T(3)), or 10(-7) mol L(-1) L: -thyroxine (T(4)). This resulted in decreasing neuronal cell number starting 48 h after treatment. T(3) -related cytotoxicity was also documented by measurement of lactate dehydrogenase release into the medium and by propidium iodide staining. Treatment of cells with 10(-7) mol L(-1) T(3) resulted in a significant increase in THRP mRNA levels as early as 24 h of treatment in a concentration-dependent manner. T(3) treatment did not alter glyceraldehyde 3-phosphate dehydrogenase (G3PDH) mRNA levels. Exogenous expression of THRP by transfecting cells with a THRP expression construct (pSVL-THRP) was associated with a significant increase in cell death as measured by the increased number of propidium iodide staining cells (18.0+/-2.1 cells per field) compared with mock-transfected cells (3.3+/-0.2), P<0.002. To further document THRP-induced cytotoxicity, the cells were either transfected with pSVL (empty vector)+pSV2neo (neomycin resistance vector for cell labeling), pSVL-THRP+pSV2neo, or pSVL-THRP+pc-Abl (cAbl tyrosine kinase expressing vector)+pSV2neo. After 24 h the cells were treated with 500 microg mL(-1) G418 (a congener of neomycin) to eliminate the non-transfected cells. Transfection with pSVL-THRP reduced neuronal survival relative to cells transfected with pSVL (356+/-15.6 compared with 145+/-16.9, P<0.05). Co-transfection of THRP with wild-type c-Abl did not alter the effect of THRP on cell survival. It is concluded that THRP is an important factor in TH-induced neuronal cell death.
Authors:
Michael J Haas; Miriam Fishman; Amjad Mreyoud; Arshag D Mooradian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-10-15
Journal Detail:
Title:  Experimental brain research     Volume:  160     ISSN:  0014-4819     ISO Abbreviation:  Exp Brain Res     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-14     Completed Date:  2005-06-30     Revised Date:  2013-12-13    
Medline Journal Info:
Nlm Unique ID:  0043312     Medline TA:  Exp Brain Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  424-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Count
Cell Death / drug effects,  physiology
Cell Survival / drug effects,  genetics
Cells, Cultured
Cerebral Cortex / cytology,  drug effects,  metabolism*
Dose-Response Relationship, Drug
Gene Expression / drug effects,  physiology
Genetic Vectors
Lactate Dehydrogenases / metabolism
Neurons / drug effects,  metabolism*
Neurotoxins / toxicity
Nuclear Proteins
Proteins / genetics,  metabolism*
RNA, Messenger / metabolism
Rats
Rats, Inbred F344
Thyroid Hormones / toxicity*
Thyroxine / toxicity
Transcription Factors
Transfection
Triiodothyronine / toxicity
Chemical
Reg. No./Substance:
0/Neurotoxins; 0/Nuclear Proteins; 0/Proteins; 0/RNA, Messenger; 0/THRSP protein, human; 0/Thrsp protein, rat; 0/Thyroid Hormones; 0/Transcription Factors; 06LU7C9H1V/Triiodothyronine; EC 1.1.-/Lactate Dehydrogenases; Q51BO43MG4/Thyroxine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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