PMID- 25304970 OWN - NLM STAT- MEDLINE DCOM- 20160302 LR - 20171116 IS - 1477-0903 (Electronic) IS - 0960-3271 (Linking) VI - 34 IP - 6 DP - 2015 Jun TI - Expression of selected proteins of the extrinsic and intrinsic pathways of apoptosis in human leukocytes exposed to N-nitrosodimethylamine. PG - 591-600 LID - 10.1177/0960327114551391 [doi] AB - N-nitrosodimethylamine (NDMA) is a xenobiotic widespread in human environment capable of regulating the lifespan of immune cells. In this study, we examined the roles of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptor 5 (DR5) complex and the Fas molecule in the induction of the extrinsic apoptosis pathway in human neutrophils (polymorphonuclear neutrophils (PMNs)) and peripheral blood mononuclear cells (PBMCs) exposed to NDMA. Also we assessed these proteins ability to trigger the intrinsic apoptosis pathway in those cells. For this purpose, we examined the expression of Fas-associated protein with death domain, truncated Bid (tBid) proteins, and apoptogenic factors such as apoptosis-inducing factor, Smac/Diablo, Omi/HtrA2, and caspase-3 as an indication of accomplished apoptosis phenomenon. PMNs and PBMCs were isolated from whole blood by density gradient centrifugation using Polymorphrep. Apoptotic cells were assessed with flow cytometry using a ready-made kit. The expression of proapoptotic molecules was investigated by Western blot analysis of PMNs and PBMCs treated with NDMA and/or rhTRAIL. The obtained results confirm the proapoptotic effects of NDMA on the examined human leukocytes and indicate an active participation of the TRAIL/DR5 complex and Fas protein in the process of apoptosis. Moreover, the research revealed distinct mechanisms of intrinsic apoptosis pathway activation between PMNs and PBMCs exposed to NDMA, as confirmed by the different levels of tBid, Smac/Diablo, Omi/HtrA2, and caspase-3 expression in those cells. CI - (c) The Author(s) 2014. FAU - Iwaniuk, A AU - Iwaniuk A AD - Department of Immunology, Medical University of Bialystok, Poland agnieszka.iwaniuk@umb.edu.pl. FAU - Jablonska, E AU - Jablonska E AD - Department of Immunology, Medical University of Bialystok, Poland. FAU - Jablonski, J AU - Jablonski J AD - Department of Toxicology, Medical University of Bialystok, Poland. FAU - Ratajczak-Wrona, W AU - Ratajczak-Wrona W AD - Department of Immunology, Medical University of Bialystok, Poland. FAU - Garley, M AU - Garley M AD - Department of Immunology, Medical University of Bialystok, Poland. LA - eng PT - Journal Article DEP - 20141010 PL - England TA - Hum Exp Toxicol JT - Human & experimental toxicology JID - 9004560 RN - 0 (FAS protein, human) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (fas Receptor) RN - M43H21IO8R (Dimethylnitrosamine) SB - IM MH - Adult MH - Apoptosis/physiology MH - Cells, Cultured MH - Dimethylnitrosamine/*toxicity MH - Female MH - Humans MH - Leukocytes, Mononuclear/*drug effects/metabolism MH - Male MH - Neutrophils/*drug effects/metabolism MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism MH - TNF-Related Apoptosis-Inducing Ligand/metabolism MH - Young Adult MH - fas Receptor/metabolism OTO - NOTNLM OT - Apoptosis/cell death OT - N-nitrosodimethylamine OT - neutrophils OT - peripheral blood mononuclear cells EDAT- 2014/10/12 06:00 MHDA- 2016/03/05 06:00 CRDT- 2014/10/12 06:00 PHST- 2014/10/12 06:00 [entrez] PHST- 2014/10/12 06:00 [pubmed] PHST- 2016/03/05 06:00 [medline] AID - 0960327114551391 [pii] AID - 10.1177/0960327114551391 [doi] PST - ppublish SO - Hum Exp Toxicol. 2015 Jun;34(6):591-600. doi: 10.1177/0960327114551391. Epub 2014 Oct 10.