Short reportExpression patterns of peroxiredoxin genes in bronchial epithelial cells exposed to diesel exhaust particles
Introduction
The epithelial cells of the airways are an important link between the environment and internal structures of the human body. Consequently, the air quality influences a number of physiological functions causing increased morbidity and mortality (Schraufnagel et al., 2019). The deterioration in air quality is mainly caused by rapid industrialization, urbanization, population growth, low quality of fuel, and usage of old motors in developing countries. Among all existing internal combustion engines, the diesel engine is a major concern in relation to the environment and public health, as it is the most popular engine and responsible for a large part of urban particulate matter. (Yang et al., 2015; Steiner et al., 2016; Sunil et al., 2017).
Diesel engines constitute a major source of particulate matter released into the air in urban environments as they produce diesel exhaust particles (DEP), which are considered the major components of particulate matter in the atmosphere. It is known that toxic compounds can adsorb on particle surfaces and, when activated, they can participate in redox reactions, leading to reactive oxygen species (ROS) formation. The small size of DEPs makes their reaching of deep regions in the respiratory tract and then the blood circulatory system easier leading to acute irritation, asthma-like symptoms, allergic responses, as well as higher risk for lung cancer (Steiner et al., 2016).
Several mechanisms have been suggested to explain the adverse effects of air pollutants on airways. The most consistent and widely accepted explanation of these is that atmospheric pollutants produce elevated levels of oxidants and pro-oxidants once in contact with the respiratory epithelium (Øvrevik, 2019).
Human cells have evolved several mechanisms to prevent oxidative damage caused by these oxidant molecules. Among them, superoxide dismutase (SOD) and catalase (CAT) are primary defense mechanism against HO• formation. Catalase, glutathione peroxidase (GPX) and PRDX act together to protect cells from the toxic effects of hydrogen peroxide.
Peroxirredoxins (PRDX) are important hydroperoxide detoxification enzymes. These belong to a family of cysteine-dependent peroxidases and exhibit high reactivity with hydrogen peroxide, organic hydroperoxides of DEP's and peroxynitrite. PRDX have several biological functions, ranging from regulation of cell proliferation and metabolism to pathways of cell death and aging. They facilitate the regulation of ROS by coupling with the thioredoxin/thioredoxin reductase system, playing major roles not only in peroxide defense, but also in regulating peroxide-mediated cell signaling. (Poole et al., 2011; Radyuk and Orr, 2018).
Six isoforms of PRDX have been identified in humans. PRDX1, 2 and 6 have a cytoplasmic localization. PRDX1 and 2 have been also detected in the nucleus. PRDX 3 has a mitochondrial localization. PRDX4 is transported through the endoplasmic reticulum and golgi for secretion. PRDX 5 is found either in the lysosomes or in peroxisomes (Rhee and Kil, 2017). PRDX1 and PRDX2 when exposed to high concentrations of peroxide may have the peroxidatic cysteine (CysP) hyperoxidized to cysteine sulfinic acid (CysP-SO2H), resulting in the loss of the peroxidase function of these enzymes since thioredoxin (the biological reductant) are able to reduce disulfides but not the hyperoxidized intermediates (Barranco-Medina et al., 2009, Rhee and Woo, 2011; Veal et al., 2018). While disulfide oxidized enzymes are dimers the hyperoxidized species are decamers or higher molecular weight (HMW) oligomers that presents molecular chaperone activity and are able to protect other important proteins from inactivation by oxidative unfolding (Ni and Lee, 2007).
On the other hand, since that the PRDX1 and PRDX2 are very abundant proteins its hyperoxidation also allow the availability of reduced thioredoxin to participate of another protective signaling pathways related to cell survival or apoptosis (Rhee and Woo, 2011; Veal et al., 2018). Is important to mention, that CysP-SO2H can be specifically reduced by sulfiredoxin (Srx) an enzyme that are able to reduce specifically CysP-SO2H restoring the peroxidase activity and favoring the dissociation of HMW complexes (Veal et al., 2018). Nevertheless, the CP-SO2H reduction rates by Srx is very slow when compared to the disulfide reduction by Trx (Mishra et al., 2015) suggesting an important physiological role of Prx hyperoxidized species.
In fact, under very harsh oxidative conditions the 2-Cys Prx can be hyperoxidized to cysteine sulfonic acid (CysP-SO3H) a species that is not reduced by sulfuredoxin and are removed of the cell by proteolysis (Lim et al., 2008).Although several studies have demonstrated that exposure to DEPs could alter the expression of genes involved in the activation of a range of intracellular transduction pathways linked to apoptosis or oxidative stress, the role played by PRDX in this process remains unknown. Therefore, this study was undertaken to evaluate the expression patterns of PDRX 1, 2, 3, 4, 5 and 6 antioxidant enzymes in BEAS-2B cells when exposed to 15 μg/mL of DEPs for either one or two hours.
Section snippets
DEP collection and chemical characterization
Diesel particles were collected from the exhaust pipe of a bus after 1 day of routine operation in the São Paulo metropolitan region. The vehicle was running on a Mercedes Benz MB1620 210-hp engine and following Euro III emission norms. There was no electronic control of fuel injection used in the engine. Any post-treatment of emissions collected from the exhaust pipe was also not performed. The diesel used contained 500 ppm of Sulfur. The diesel collected was stored for toxicological analysis
Results and discussion
Here we report that the expression levels of PRDX2, PRDX5 and PRDX6 genes are down regulated in BEAS-2B cells after 1 h of exposure to DEPs, suggesting that the effects observed in our previous studies (Seriani et al., 2015b) could be correlated with the results obtained in the present study. Using qPCR, we evaluated the transcription levels of all the six isoforms of PRDX in BEAS-2B cells after one or two hours of exposure to DEPs. We observed that the mRNA levels of PRDX2, PRDX5 and PRDX6
Acknowledgments
This study was supported financially by the São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP), Process No. 2011/50334-7. We would like to thank Dr. Carla Lima, and Marcio José Ferreira (Butantã Institute, São Paulo) and Thiago Franco Oliveira (Federal University of Health Sciences of Porto Alegre (UFCSPA)) and Ana Paula Loureiro (University of São Paulo College of Pharmaceutical Sciences, Department of Clinical and Toxicological Analysis) for their
References (45)
- et al.
Overexpression of human peroxiredoxin 5 in subcellular compartments of Chinese hamster ovary cells: effects on cytotoxicity and DNA damage caused by peroxides
Free Radic. Biol. Med.
(2004) - et al.
The oligomeric conformation of peroxiredoxins links redox state to function
FEBS Lett
(2009) - et al.
1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities
J. Biol. Chem.
(2000) - et al.
Peroxiredoxin-2 plays a pivotal role as multimodal cytoprotector in the early phase of pulmonary hypertension
Free Radic. Biol. Med.
(2017) Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling
Arch Biochem. Biophys.
(2017)- et al.
Thioredoxin-1 redox signaling regulates cell survival in response to hyperoxia
Free Radic. Biol. Med.
(2014) - et al.
Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation
J. Biol. Chem.
(2013) - et al.
Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity
J. Biol. Chem.
(2008) - et al.
Peroxiredoxin 6, a 1-Cys peroxiredoxin, functions in antioxidant defense and lung phospholipid metabolism
Free Radic. Biol. Med.
(2005) - et al.
The sulfiredoxin–peroxiredoxin (Srx–Prx) axis in cell signal transduction and cancer development
Cancer Lett
(2015)
Human peroxiredoxin 5 gene organization, initial characterization of itspromoter and identifcation of alternative forms of mRNA
Biochim. Biophys. Acta Gene Struct. Expr.
ER chaperones in mammalian development and human diseases
FEBS Lett
Peroxiredoxin interaction with the cytoskeletal-regulatory protein CRMP2: investigation of a putative redox relay
Free Radic. Biol. Med.
Air pollution and noncommunicable diseases: a review by the forum of international respiratory societies’ environmental committee, part 2: air pollution and organ systems
Chest.
Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells
Exp. Toxicol. Pathol.
The impact of early-life exposure to air-borne environmental insults on the function of the airway epithelium in asthma
Ann. Global Health
World trade center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung
Exp. Mol. Pathol.
Mitochondrial OGG1 protects against PM2. 5-induced oxidative DNA damage in BEAS-2B cells
Exp. Mol. Pathol.
Overexpression of antioxidant enzyme peroxiredoxin 5 protects human tendon cells against apoptosis and loss of cellular function during oxidative stress
Biochim. Biophys. Acta
Time-course effects of antioxidants and phase II enzymes on diesel exhaust particles-induced oxidative damage in the mouse lung
Toxicol. Appl. Pharmacol.
The role of peroxiredoxin 6 in cell signaling
Antioxidants (Basel).
Macromolecular Protein Complexes
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