| Association of Metals and Proteasome Activity in Erythrocytes of Prostate Cancer Patients and Controls. | |
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MedLine Citation:
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PMID: 22422614 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-3-16 |
Journal Detail:
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Title: Biological trace element research Volume: - ISSN: 1559-0720 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7911509 Medline TA: Biol Trace Elem Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA, cdudas1@hfhs.org. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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