Effect of Polyaryl Hydrocarbons on Cytotoxicity in Monocytic Cells: Potential Role of Cytochromes P450 and Oxidative Stress Pathways

Ranjit, Sabina; Midde, Narasimha M.; Sinha, Namita; Patters, Benjamin J.; Rahman, Mohammad Arifur; Cory, Theodore J.; Rao, P.S.S.; Kumar, Santosh

doi:10.1371/journal.pone.0163827

Cited by 36 publications

(44 citation statements)

References 52 publications

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“…to benzo(a)pyrene produced reactive oxygen species, which was accompanied by caspase-3 activation and apoptotic cell death (14). Taken together, the findings of those studies suggest that the toxic effect of PAHs likely occurs through the oxidative stress pathway.…”

Section: Transformation Of Liver Cells By 3-methylcholanthrene Potentmentioning

confidence: 70%

Transformation of liver cells by 3-methylcholanthrene potentiates oxidative stress via the downregulation of glutathione synthesis

et al. 2017

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Polycyclic aromatic hydrocarbons (PAHs) are widespread contaminants resulting from the incomplete combustion of organic materials in the environment. The primary concern for the hazardous effect of PAHs is their ability to activate the pathway linked to the aryl hydrocarbon receptor (AhR) and lead to carcinogenesis. While previous research has demonstrated that oxidative stress plays a key role in the AhR-dependent toxic response, the effect of PAHs on the biosynthesis of glutathione (GSH), which is a powerful endogenous antioxidant, has not been extensively investigated. In the present study, we utilized a global metabolomic approach, via high resolution magic angle spinning nuclear magnetic resonance spectroscopy, and identified significant metabolome differences between non-tumorigenic liver cells (BNL CL.2; CL2) and transformed liver cells (BNL 1MEA. 7R.1; 1MEA) chronically exposed to 3-methylcholanthrene (3MC), a well‑known carcinogenic PAH. A significant change that was observed, was a lower GSH level in 1MEA cells compared with that in CL2 cells. This was contrasted by increased levels of precursor metabolites for GSH synthesis, such as S-adenosylmethionine and cysteine. These changes were accompanied by a significantly reduced expression of γ-glutamylcysteine ligase (GCL), known to be the rate‑limiting step of GSH synthesis. Furthermore, the protein level of cysteine dioxygenase was downregulated; however, the concentration of taurine was unaltered. Therefore, the present study demonstrated that cells transformed by chronic exposure to 3MC exhibited inhibition of GSH biosynthesis by suppression of GCL protein expression and reduction of cysteine availability, which may subsequently render cells vulnerable to oxidative stress.

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Section: Transformation Of Liver Cells By 3-methylcholanthrene Potentmentioning

confidence: 70%

Transformation of liver cells by 3-methylcholanthrene potentiates oxidative stress via the downregulation of glutathione synthesis

et al. 2017

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“…The reason for a decrease in protein expression, despite increased mRNA expression, could be due to various transcriptional and post-translational modifications, differential stability of mRNAs versus proteins, or due to interference by different miRNAs [53,54]. This is consistently the case for CYP1A1 expression upon exposure to cigarette smoke condensate and benzo(a)pyrene [23,48].…”

Section: Discussionmentioning

confidence: 97%

“…We particularly examined the expression of CYP1A1 and CYP2A6, because these enzymes are expressed in monocytic cells. CYP1A1 and CYP2A6 are the major enzymes for metabolizing polyaryl hydrocarbons and nicotine present in cigarette smoke, respectively, as well as environmental contaminants [48,49]. The concurrent upregulation of CYPs and elevation in ROS levels suggest that the oxidative stress in U1 cells could occur via a CYP-mediated pathway.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from Human Papilloma Virus-Infected Cervical Cancer Cells Enhance HIV-1 Replication in Differentiated U1 Cell Line

Ranjit

Kumar

Sinha

et al. 2020

Viruses

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In the current study, we hypothesized that extracellular vesicles (EVs) secreted from human papilloma virus (HPV)-infected cervical cancer cells exacerbate human immunodeficiency virus (HIV)-1 replication in differentiated U1 cell line through an oxidative stress pathway. To test the hypothesis, we treated an HIV-1-infected macrophage cell line (U1) with HPV-infected Caski cell culture supernatant (CCS). We observed a significant increase in HIV-1 replication, which was associated with an increase in the expression of cytochrome P450 (CYPs 1A1 and 2A6) in the CCS-treated U1 cells. Furthermore, we isolated EVs from CCS (CCS-EVs), which showed the presence of CYPs (1A1, 2A6), superoxide dismutase 1 (SOD1), and HPV oncoproteins HPV16 E6. CCS-EVs when exposed to the U1 cells also significantly increased HIV-1 replication. Treatment of antioxidant, CYP1A1 and CYP2A6 inhibitors, and chemodietary agents with antioxidant properties significantly reduced the CCS and CCS-EVs mediated HIV-1 replication in U1 cells. Altogether, we demonstrate that cervical cancer cells exacerbate HIV-1 replication in differentiated U1 cell line via transferring CYPs and HPV oncoproteins through EVs. We also show that the viral replication occurs via CYP and oxidative stress pathways, and the viral replication is also reduced by chemodietary agents. This study provides important information regarding biological interactions between HPV and HIV-1 via EVs leading to enhanced HIV-1 replication.Viruses 2020, 12, 239 2 of 20 largely unknown. Therefore, there is a need to examine the biological interactions between HPV and HIV-1 to find better preventive and treatment strategies to reduce HIV-1 pathogenesis in HIV-1/HPV coinfected individuals.Evidences from previous reports show that cervical cancer cells constantly undergo oxidative stress [6][7][8]. Clinical samples from cervical cancer patients reveal a higher reactive oxygen species (ROS) level, higher oxidative damage, and a lower level of antioxidants, compared to samples from healthy individuals [9][10][11]. In vitro experiments also suggest a high level of ROS, profound downregulation in the genes associated with antioxidant proteins, such as superoxide dismutase 1 (SOD1), SOD2, SOD3, peroxiredoxin 1 (PRDX1), PRDX2, glutathione S-synthetase (GSS), and glutathione peroxidase 6 (GPX6), and high presence of Poly [ADP-ribose] polymerase 1 (PARP1), a marker of oxidative stress-induced DNA damage in cervical carcinoma-derived Caski cells [7]. HPV oncoproteins E6 and E7 stimulate the degradation of tumor-suppressor p53 protein [12], causing uncontrolled cell growth. The p53 protein, which primarily attributes to apoptosis and genomic stability, is also reported to have an antioxidant role [13]. Downregulation of p53 suppresses its antioxidant potential and renders the cells vulnerable to oxidative damage. Furthermore, the expression of HPV E6 and E7 oncoproteins alone is sufficient to cause oxidative stress. Marullo et al. demonstrated that HPV E6 and E7 proteins generate a chronic oxidative respo...

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“…the likely sources of Th17-promoting activity (39) . Cigarette smoke contains substantial PAHs (22) . Taken together, IL-17A-mediated inflammation via AhR activation induced by cigarette smoke contributed to corticosteroid resistance and airway flow obstruction in patients with asthma.…”

Section: Asthma and Crsmentioning

confidence: 99%

“…This AhR-ARNT complex binds to a dioxin-responsive element and initiates the transcription of genes that comprise the AhR gene battery, including cytochrome P450 family and cyclooxygenase-2 enzymes (COX-2) (20,21) . PAH is an important constituent of cigarette smoke that triggers AhR activation (22,23) . Activation of AhR may be essential for the differentiation of ILC3 and Th17 cells, as well as the consequent IL-17A-mediated immune response (24,25) .…”

Section: Introductionmentioning

confidence: 99%

Impact of cigarette smoke and IL-17A activation on asthmatic patients with chronic rhinosinusitis

Lee

et al. 2019

Rhin

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Background: Cigarette smoke have adverse effects in the control of asthma and chronic rhinosinusitis (CRS). Interleukin (IL)-17A, the signature cytokine of helper T 17 cells and group 3 innate lymphoid cells (ILC3), has been reported to link with resistance to therapy in airway inflammation. This study aimed to investigate the impact of cigarette smoking and IL-17A activation on the clinical outcomes of asthmatic patients with chronic rhinosinusitis. Methods: 33 patients with CRS and asthma, including 15 smokers and 18 non-smokers, and 7 asthmatic patients without CRS and smoking were prospectively recruited. The Sino-Nasal Outcome Test-22 and Asthma Control Test were used to evaluate sinonasal symptoms and the level of asthma control, respectively. Real-time PCR and immunostaining were applied to evaluate the expression levels of IL-17A and associated immunological factors on surgically-obtained nasal tissues. Results: Nasal surgery improved both sinonasal symptoms and asthma control. Compared to non-smokers, smokers showed poorer improvement in asthma control. The expression of IL-17A, IL-22, aryl hydrocarbon receptor (AhR), and ILC3 was increased in the nasal tissues of smokers with asthma and CRS. The expression of IL-17A mRNA was correlated with that of AhR and with positive nuclear AhR-AhR nuclear translocator staining cells, and that of cyclooxygenase-2 enzyme (COX-2). ILC3 cells were associated with IL-17A, IL-22, AhR, and COX-2 mRNA expression. Conclusions: Cigarette smoking was related to lesser improvement in asthma control after nasal surgery and to IL-17A activation in the nasal tissues of patients with inflammatory airways.

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Effect of Polyaryl Hydrocarbons on Cytotoxicity in Monocytic Cells: Potential Role of Cytochromes P450 and Oxidative Stress Pathways

Cited by 36 publications

References 52 publications

Transformation of liver cells by 3-methylcholanthrene potentiates oxidative stress via the downregulation of glutathione synthesis

Transformation of liver cells by 3-methylcholanthrene potentiates oxidative stress via the downregulation of glutathione synthesis

Extracellular Vesicles from Human Papilloma Virus-Infected Cervical Cancer Cells Enhance HIV-1 Replication in Differentiated U1 Cell Line

Impact of cigarette smoke and IL-17A activation on asthmatic patients with chronic rhinosinusitis

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