The Identification of Cocaine-Induced Changes in the Human Monocyte Proteome Using Isotope-Coded Affinity Tags

Date of Award

2008

Document Type

Thesis

Degree Name

Bachelors

Department

Natural Sciences

First Advisor

Walstrom, Katherine

Keywords

ICAT, Proteomics, Cocaine, Mass Spectronetry, Monocyte

Area of Concentration

Biopsychology

Abstract

Cocaine is a widely abused drug with a broad spectrum of physiological effects. In addition to its addictive properties, cocaine has been shown to result in suppression of the immune system. In recent years, the cellular mechanisms underlying drug response and disease states have been investigated using liquid chromatography (LC) and tandem mass spectrometry (MS/MS) to map changes in protein expression in affected cells. A new technique, utilizing isotope-coded affinity tags (ICAT), allows quantitative as well as qualitative changes in protein expression to be determined by LC/MS/MS. This study sought to characterize the effects of cocaine exposure on protein expression in cultured human monocytes using these methods to investigate the mechanisms underlying cocaine-induced immunosuppression. Two proteins thought to be involved in inflammatory immune responses, pannexin 3 and macrophage migration inhibitory factor (MIF), showed decreases in abundance as a result of cocaine exposure. In addition, two proteins involved in protein synthesis, eukaryotic translation elongation factor 2(EF-2) and a homologue of 60S ribosomal protein L12, showed decreases in abundance. These results are consistent with previous findings that cocaine causes inhibition of the inflammatory immune response. A novel mechanism for cocaine-induced immunosuppression, mediated via the antagonism of muscarinic acetylcholine receptors, is proposed.

Rights

This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.

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