PMID- 20860616 OWN - NLM STAT- MEDLINE DCOM- 20110315 LR - 20211020 IS - 1530-0277 (Electronic) IS - 0145-6008 (Print) IS - 0145-6008 (Linking) VI - 34 IP - 12 DP - 2010 Dec TI - Implications of ER stress, the unfolded protein response, and pro- and anti-apoptotic protein fingerprints in human monocyte-derived dendritic cells treated with alcohol. PG - 2081-8 LID - 10.1111/j.1530-0277.2010.01304.x [doi] AB - BACKGROUND: Dendritic cells (DCs) are responsible for the activation of T cells and B cells. There is accumulating evidence that psychoactive substances such as alcohol can affect immune responses. We hypothesize that this occurs by modulating changes in proteins triggering a process known as unfolded protein response (UPR). This process protects cells from the toxic effects of misfolded proteins responsible for causing endoplasmic reticulum (ER) stress. Although much is known about ER stress, little is understood about the consequences of ethanol use on DC's protein expression. METHODS: In this study, we investigated alterations in the proteins of human monocyte-derived dendritic cells (MDDC) treated with 0.1% of alcohol by two-dimensional (2D) gel electrophoresis followed by liquid chromatography-tandem mass spectrometry, protein identification, and confirmation at the gene expression level by qRT-PCR. RESULTS: Proteomes of related samples demonstrated 32 differentially expressed proteins that had a 2-fold or greater change in expression (18 spots were up-regulated and 14 were down-regulated), compared to the control cultures (untreated cells). Alcohol significantly changed the expression of several components of the UPR stress-induced pathways that include chaperones, ER stress, antioxidant enzymes, proteases, alcohol dehydrogenase, cytoskeletal and apoptosis-regulating proteins. qRT-PCR analyses highlighted the enhanced expression of UPR and antioxidant genes that increased (18 hours) with alcohol treatment. CONCLUSION: Results of these analyses provide insights into alcohol mechanisms of regulating DC and suggest that alcohol induced specifically the UPR in DC. We speculate that activation of a UPR by alcohol may protect the DC from oxidant injury but may lead to the development of alcohol-related diseases. CI - Copyright (c) 2010 by the Research Society on Alcoholism. FAU - Boukli, Nawal M AU - Boukli NM AD - Biomedical Proteomics Facility, Department of Microbiology and Immunology, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico, USA. FAU - Saiyed, Zainulabedin M AU - Saiyed ZM FAU - Ricaurte, Martha AU - Ricaurte M FAU - Rodriguez, Jose W AU - Rodriguez JW FAU - Rios Olivares, Eddy AU - Rios Olivares E FAU - Cubano, Luis A AU - Cubano LA FAU - Nair, Madhavan P N AU - Nair MP LA - eng GR - R01 MH085259/MH/NIMH NIH HHS/United States GR - R01 AA017405/AA/NIAAA NIH HHS/United States GR - R01 DA021537/DA/NIDA NIH HHS/United States GR - G12 MD007583/MD/NIMHD NIH HHS/United States GR - R01 DA012366-11/DA/NIDA NIH HHS/United States GR - R37DA025576/DA/NIDA NIH HHS/United States GR - G11 HD052352/HD/NICHD NIH HHS/United States GR - R01 DA027049/DA/NIDA NIH HHS/United States GR - S06GM050695/GM/NIGMS NIH HHS/United States GR - G11HD052352/HD/NICHD NIH HHS/United States GR - R01DA027049/DA/NIDA NIH HHS/United States GR - R01DA021537/DA/NIDA NIH HHS/United States GR - R01 DA027049-03/DA/NIDA NIH HHS/United States GR - 2G12RR03035/RR/NCRR NIH HHS/United States GR - R01AA017405/AA/NIAAA NIH HHS/United States GR - R01DA012366/DA/NIDA NIH HHS/United States GR - R01 DA012366/DA/NIDA NIH HHS/United States GR - R01 MH085259-02/MH/NIMH NIH HHS/United States GR - R37 DA025576-03/DA/NIDA NIH HHS/United States GR - S06 GM050695/GM/NIGMS NIH HHS/United States GR - R01 DA021537-06/DA/NIDA NIH HHS/United States GR - G12 RR003035/RR/NCRR NIH HHS/United States GR - R37 DA025576/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100922 PL - England TA - Alcohol Clin Exp Res JT - Alcoholism, clinical and experimental research JID - 7707242 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Proteome) RN - 3K9958V90M (Ethanol) SB - IM MH - Apoptosis Regulatory Proteins/*metabolism MH - Cells, Cultured MH - Dendritic Cells/drug effects/*metabolism MH - Endoplasmic Reticulum/drug effects/*metabolism MH - Ethanol/*pharmacology MH - Gene Expression/drug effects MH - Humans MH - Proteome/drug effects MH - Stress, Physiological/*drug effects MH - Unfolded Protein Response/*drug effects PMC - PMC2988982 MID - NIHMS225615 EDAT- 2010/09/24 06:00 MHDA- 2011/03/16 06:00 PMCR- 2011/12/01 CRDT- 2010/09/24 06:00 PHST- 2010/09/24 06:00 [entrez] PHST- 2010/09/24 06:00 [pubmed] PHST- 2011/03/16 06:00 [medline] PHST- 2011/12/01 00:00 [pmc-release] AID - 10.1111/j.1530-0277.2010.01304.x [doi] PST - ppublish SO - Alcohol Clin Exp Res. 2010 Dec;34(12):2081-8. doi: 10.1111/j.1530-0277.2010.01304.x. Epub 2010 Sep 22.