Proteomic analyses of the effects of drugs of abuse on monocyte-derived mature dendritic cells.
Drug abuse has become a global health concern. Understanding how drug abuse modulates the immune system and how the immune system responds to pathogens associated with drug abuse, such hepatitis C virus (HCV) and human immunodeficiency virus (HIV-1), can be assessed by an integrated approach comparing proteomic analyses and quantitation of gene expression. Two-dimensional (2D) difference gel electrophoresis was used to determine the molecular mechanisms underlying the proteomic changes that alter normal biological processes when monocyte-derived mature dendritic cells were treated with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins including those that modulate apoptosis, protein folding, protein kinase activity, and metabolism and proteins that function as intracellular signal transduction molecules. Proteomic data were validated using a combination of quantitative, real-time PCR and Western blot analyses. These studies will help to identify the molecular mechanisms, including the expression of several functionally important classes of proteins that have emerged as potential mediators of pathogenesis. These proteins may predispose immunocompetent cells, including dendritic cells, to infection with viruses such as HCV and HIV-1, which are associated with drug abuse.
Reynolds
Jessica L
JL
Departments of Medicine, Division of Allergy, Immunology and Rheumatology, State University of New York at Buffalo, Buffalo General Hospital, Buffalo, New York, USA. jlr8@buffalo.edu
Mahajan
Supriya D
SD
Aalinkeel
Ravikunar
R
Nair
B
B
Sykes
Donald E
DE
Schwartz
Stanley A
SA
D002454:Cell Differentiation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D015497:HIV-1; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000276:immunology / Q000821:virology; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008694:Methamphetamine / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D020543:Proteome; D040901:Proteomics; D019966:Substance-Related Disorders / Q000150:complications*
D011506:Proteins; D020543:Proteome; D008694:Methamphetamine; D003042:Cocaine