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Association of Metals and Proteasome Activity in Erythrocytes of Prostate Cancer Patients and Controls

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Abstract

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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Acknowledgements

Wayne State University President’s Research Enhancement Program, NIEHS 5R01 ES011126, CDMRP W81XWH-07-1-0252

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Authors and Affiliations

  1. Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA

    Christine Neslund-Dudas & Benjamin A. Rybicki

  2. Population Studies and Disparities Research, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Christine Neslund-Dudas & Benjamin A. Rybicki

  3. Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI, USA

    Bharati Mitra & Ashoka Kandegedara

  4. Department of Pharmacology and Pathology, Wayne State University School of Medicine, Detroit, MI, USA

    Di Chen, Sara Schmitt, Min Shen, Qiuzhi Cui & Q. Ping Dou

  5. Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA

    Q. Ping Dou

  6. Developmental Therapeutics Programs, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Q. Ping Dou

  7. Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, Suite 5C, Detroit, MI, 48202, USA

    Christine Neslund-Dudas

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  1. Christine Neslund-Dudas
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  2. Bharati Mitra
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  3. Ashoka Kandegedara
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  7. Qiuzhi Cui
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  8. Benjamin A. Rybicki
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  9. Q. Ping Dou
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Correspondence to Christine Neslund-Dudas.

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Neslund-Dudas, C., Mitra, B., Kandegedara, A. et al. Association of Metals and Proteasome Activity in Erythrocytes of Prostate Cancer Patients and Controls. Biol Trace Elem Res 149, 5–9 (2012). https://doi.org/10.1007/s12011-012-9391-z

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  • DOI: https://doi.org/10.1007/s12011-012-9391-z

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