Document Detail

Zinc adaptation and resistance to cadmium toxicity in mammalian cells: molecular insight by proteomic analysis.
MedLine Citation:
PMID:  18452231     Owner:  NLM     Status:  MEDLINE    
To identify proteins involved in cellular adaptive responses to zinc, a comparative proteome analysis between a previously developed high zinc- and cadmium-resistant human epithelial cell line (high zinc-resistant HeLa cells, HZR) and the parental HeLa cells has been carried out. Differentially produced proteins included cochaperones, proteins associated with oxido-reductase activities, and ubiquitin. Biochemical pathways to which these proteins belong were probed for their involvement in the resistance of both cell lines against cadmium toxicity. Among ER stressors, thapsigargin sensitized HZR cells, but not HeLa cells, to cadmium toxicity more acutely than tunicamycin, implying that these cells heavily relied on proper intracellular calcium distribution. The similar sensitivity of both HeLa and HZR cells to inhibitors of the proteasome, such as MG-132 or lactacystin, excluded improved proteasome activity as a mechanism associated with zinc adaptation of HZR cells. The enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) was overproduced in HZR cells as compared to HeLa cells. It transforms HPP to homogentisate in the second step of tyrosine catabolism. Inhibition of HPPD decreased the resistance of HZR cells against cadmium, but not that of HeLa cells, suggesting that adaptation to zinc overload and increased HPP removal are linked in HZR cells.
Estelle Rousselet; Alain Martelli; Mireille Chevallet; Hélène Diemer; Alain Van Dorsselaer; Thierry Rabilloud; Jean-Marc Moulis
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proteomics     Volume:  8     ISSN:  1615-9861     ISO Abbreviation:  Proteomics     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-10     Completed Date:  2008-09-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101092707     Medline TA:  Proteomics     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2244-55     Citation Subset:  IM    
CEA, DSV, IRTSV, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
4-Hydroxyphenylpyruvate Dioxygenase / metabolism
Cadmium / chemistry,  pharmacology,  toxicity*
Cadmium Poisoning / metabolism
Carbonic Anhydrases / metabolism
Cell Survival
Dose-Response Relationship, Drug
Electrophoresis, Gel, Two-Dimensional
Epithelial Cells / cytology
Hela Cells
Proteomics / methods*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tetrazolium Salts / pharmacology
Thiazoles / pharmacology
Zinc / chemistry*
Reg. No./Substance:
0/Proteome; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; 7440-43-9/Cadmium; 7440-66-6/Zinc; EC Dioxygenase; EC Anhydrases

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

Previous Document:  Immobilization strategies for single-chain antibody microarrays.
Next Document:  Proteomic analysis of the chicken egg vitelline membrane.