Document Detail


Association of metals and proteasome activity in erythrocytes of prostate cancer patients and controls.
MedLine Citation:
PMID:  22422614     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Information is lacking on the effects toxic environmental metals may have on the 26S proteasome. The proteasome is a primary vehicle for selective degradation of damaged proteins in a cell and due to its role in cell proliferation, inhibition of the proteasome has become a target for cancer therapy. Metals are essential to the proteasome's normal function and have been used within proteasome-inhibiting complexes for cancer therapy. This study evaluated the association of erythrocyte metal levels and proteasome chymotrypsin-like (CT-like) activity in age- and race-matched prostate cancer cases (n=61) and controls (n=61). Erythrocyte metals were measured by inductively coupled plasma mass spectrometry (ICP-MS). CT-like activity was measured by proteasome activity assay using a fluorogenic peptide substrate. Among cases, significant correlations between individual toxic metals were observed (r(arsenic-cadmium)=0.49, p<0.001; r(arsenic-lead)=0.26, p=0.04, r(cadmium-lead) 0.53, p<0.001), but there were no significant associations between metals and CT-like activity. In contrast, within controls there were no significant associations between metals, however, copper and lead levels were significantly associated with CT-like activity. The associations between copper and lead and proteasome activity (r(copper-CT-like)=-0.28, p=0.002 ; r(lead-CT-like)=0.23, p=0.011) remained significant in multivariable models that included all of the metals. These findings suggest that biologically essential metals and toxic metals may affect proteasome activity in healthy controls and, further, show that prostate cancer cases and controls differ in associations between metals and proteasome activity in erythrocytes. More research on toxic metals and the proteasome in prostate cancer is warranted.
Authors:
Christine Neslund-Dudas; Bharati Mitra; Ashoka Kandegedara; Di Chen; Sara Schmitt; Min Shen; Qiuzhi Cui; Benjamin A Rybicki; Q Ping Dou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-03-16
Journal Detail:
Title:  Biological trace element research     Volume:  149     ISSN:  1559-0720     ISO Abbreviation:  Biol Trace Elem Res     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-07     Completed Date:  2013-01-18     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  7911509     Medline TA:  Biol Trace Elem Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5-9     Citation Subset:  IM    
Affiliation:
Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA. cdudas1@hfhs.org
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Arsenic / metabolism,  toxicity
Cadmium / metabolism,  toxicity
Case-Control Studies
Chymotrypsin / metabolism
Copper / metabolism,  toxicity
Environmental Exposure / analysis
Enzyme Activation
Erythrocytes / enzymology,  metabolism*
Gene-Environment Interaction
Humans
Lead / metabolism,  toxicity
Male
Mass Spectrometry / methods
Middle Aged
Multivariate Analysis
Prostatic Neoplasms / enzymology,  pathology*
Proteasome Endopeptidase Complex / metabolism*
Grant Support
ID/Acronym/Agency:
5R01 ES011126/ES/NIEHS NIH HHS; R01 ES011126/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
7439-92-1/Lead; 7440-38-2/Arsenic; 7440-43-9/Cadmium; 7440-50-8/Copper; EC 3.4.21.1/Chymotrypsin; EC 3.4.25.1/Proteasome Endopeptidase Complex; EC 3.4.99.-/ATP dependent 26S protease
Comments/Corrections

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


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