Benzo[a]pyrene induces oxidative stress and endothelial progenitor cell dysfunction via the activation of the NF-κB pathway

Abstract

Smoking is a major risk factor for atherosclerosis. In this study, we evaluated the effects of benzo[a]pyrene (BaP, a prominent component of tobacco smoke) on the function and pro-inflammatory response of human endothelial progenitor cells (EPCs). EPCs were isolated from umbilical cord blood and treated with different concentrations (10, 20 and 50 µmol/l) of BaP. The proliferation, migration, adhesion and angiogenesis of BaP-treated EPCs were evaluated using the cell counting kit-8 (CCK-8), Transwell assay, adhesion assay and in vitro tube formation assay, respectively. The activation of nuclear factor-κB (NF-κB) was evaluated by measuring the mRNA expression of NF-κB p65 and p50 by real-time RT-PCR and NF-κB translocation assay. Reactive oxygen species (ROS) production was determined by the reduction of fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). The results demonstrated that BaP treatment significantly inhibited the proliferation, migration, adhesion and angiogenesis of EPCs in vitro. In addition, BaP induced the release of interleukin (IL)-1β and tumor necrosis factor-α from these cells. Moreover, the exposure of EPCs to BaP induced ROS generation and the activation of NF-κB. Experiments with EPCs pre-treated with pyrrolidine dithiocarbamate, an inhibitor of NF-κB, revealed that the BaP-mediated inhibition of proliferation, migration, adhesion and angiogenesis of EPCs is mainly regulated by NF-κB. Thus, tobacco smoke may induce oxidant-mediated stress responses in EPCs and impair their function via the activation of the NF-κB pathway.

Asymmetric Dimethylarginine Induced Apoptosis and Dysfunction of Endothelial Progenitor Cells: Role of Endoplasmic Reticulum Stress Pathway

“…Immunohistochemistry staining also showed that EPCs expressed both CD34 and factor VIII (Figures 1(c) and 1(d)). These characteristics were consistent with other studies of EPCs [28]. …”

High-throughput data integration of RNA–miRNA–circRNA reveals novel insights into mechanisms of benzo[a]pyrene-induced carcinogenicity

“…Other important genes are significantly over-expressed in BaP-exposed cell at minimally 3 time points, including the detoxifying enzyme ALDH3A1 (aldehyde dehydrogenase 3), AKR1B10 , an aldo–keto reductase playing a role in carcinogenicity, or OSGIN1 (oxidative stress-induced growth inhibitor 1), an oxidative stress response gene induced by DNA damage, consistent with the observation that BaP induces reactive oxygen species (ROS) formation (23). The majority of differentially expressed genes is up-regulated and only a minority of genes is inhibited by BaP exposure (54 of the 266 DE genes at 6 h), among which are two histones genes ( HIST1H3J and HIST1H2BM ), which may point toward epigenomic changes induced by BaP exposure.…”

Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons

“…These responses are mainly mediated by the AHR/aryl hydrocarbon nuclear translocator (ARNT) signaling pathway. AHR as a nuclear factor participates in transcription factor kB (NF-kB) signaling pathways regulating inflammation, immune responses, apoptosis, survival, and other functions (Baglole et al, 2008;Puga et al, 2009;Ji et al, 2013;Nguyen et al, 2013;Quintana and Sherr, 2013). It has emerged as an endogenous regulator of COX-2 by a mechanism that is poorly understood (Baglole et al, 2008;Nguyen et al, 2013).…”

“…Several PAHs, including BaP, benzo(b)fluoranthene (Bbf), benzo(k)fluoranthene (Bkf) have caused tumors in laboratory animals. Other effects, which may influence reproduction, development, and immunity, are not well-known (Hwang et al, 2007, Ji et al, 2013Kim et al, 2013).…”