N-nitrosodimethylamine (NDMA) induced apoptosis dependent on Fas/FasL complex in human leukocytes.

Abstract:

OBJECTIVE:To investigate the mechanism of apoptosis dependent on the Fas/FasL (Fas ligand) complex in the presence of N-nitrosodimethylamine (NDMA) in human leukocytes. METHODS:Polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated form whole blood by density centrifugation. The concentration of NDMA was assessed by cellular toxicity assay. Apoptotic cells were assessed with flow cytometry and the expression of pro- and antiapoptotic proteins was investigated by Western blotting in PMNs and PBMCs treated with NDMA and/or FasL. RESULTS:PMNs showed a higher ratio of apoptotic cells than PBMCs after exposure to NDMA and/or FasL. Enhanced apoptosis was related to the increased expression of proapoptotic proteins in neutrophils following exposure to either NDMA or FasL. In PBMCs, the relation was observed after exposure to FasL only. PMNs and PBMCs incubated with NDMA and FasL simultaneously demonstrated the highest increase in protein expression. CONCLUSIONS:NDMA shows a stronger proapoptotic effect with PMNs than with PBMCs. The Fas/FasL complex, along with other proapoptotic proteins of the receptor (Fas, FADD) and mitochondrial pathway (Noxa, Puma, Bim), plays a key role in the induction of neutrophil apoptosis. Synergic effects of NDMA and FasL which lead to higher induction of apoptosis in PMNs than in PBMCs indicates a multistage and varied regulation of apoptosis in different populations of leukocytes.

journal_name

Hum Exp Toxicol

authors

Iwaniuk A,Grubczak K,Ratajczak-Wrona W,Garley M,Nowak K,Jabłońska E

doi

10.1177/0960327119828198

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

578-587

issue

5

eissn

0960-3271

issn

1477-0903

journal_volume

38

pub_type

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