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NOX4 Mediates Pseudomonas aeruginosa-Induced Nuclear Reactive Oxygen Species Generation and Chromatin Remodeling in Lung Epithelium.

ABSTRACT: Pseudomonas aeruginosa (PA) infection increases reactive oxygen species (ROS), and earlier, we have shown a role for NADPH oxidase-derived ROS in PA-mediated lung inflammation and injury. Here, we show a role for the lung epithelial cell (LEpC) NOX4 in PA-mediated chromatin remodeling and lung inflammation. Intratracheal administration of PA to Nox4^flox/flox mice for 24 h caused lung inflammatory injury; however, epithelial cell-deleted Nox4 mice exhibited reduced lung inflammatory injury, oxidative stress, secretion of pro-inflammatory cytokines, and decreased histone acetylation. In LEpCs, NOX4 was localized both in the cytoplasmic and nuclear fractions, and PA stimulation increased the nuclear NOX4 expression and ROS production. Downregulation or inhibition of NOX4 and PKC δ attenuated the PA-induced nuclear ROS. PA-induced histone acetylation was attenuated by Nox4-specific siRNA, unlike Nox2. PA stimulation increased HDAC1/2 oxidation and reduced HDAC1/2 activity. The PA-induced oxidation of HDAC2 was attenuated by N-acetyl-L-cysteine and siRNA specific for Pkc δ, Sphk2, and Nox4. PA stimulated RAC1 activation in the nucleus and enhanced the association between HDAC2 and RAC1, p-PKC δ, and NOX4 in LEpCs. Our results revealed a critical role for the alveolar epithelial NOX4 in mediating PA-induced lung inflammatory injury via nuclear ROS generation, HDAC1/2 oxidation, and chromatin remodeling.

SUBMITTER: Fu P

PROVIDER: S-EPMC8002602 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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NOX4 Mediates Pseudomonas aeruginosa-Induced Nuclear Reactive Oxygen Species Generation and Chromatin Remodeling in Lung Epithelium.

Fu Panfeng P Ramchandran Ramaswamy R Sudhadevi Tara T Kumar Prasanth P K PPK Krishnan Yashaswin Y Liu Yuru Y Zhao Yutong Y Parinandi Narasimham L NL Harijith Anantha A Sadoshima Junichi J Natarajan Viswanathan V

Antioxidants (Basel, Switzerland) 20210317 3

Pseudomonas aeruginosa (PA) infection increases reactive oxygen species (ROS), and earlier, we have shown a role for NADPH oxidase-derived ROS in PA-mediated lung inflammation and injury. Here, we show a role for the lung epithelial cell (LEpC) NOX4 in PA-mediated chromatin remodeling and lung inflammation. Intratracheal administration of PA to Nox4flox/flox mice for 24 h caused lung inflammatory injury; however, epithelial cell-deleted Nox4 mice exh ...[more]

PMID: 33802941

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Project description:BACKGROUND:Rhamnolipids are the most extensively studied biosurfactants and has been successfully used in various areas from bioremediation to industrial fields. Rhamnolipids structural composition decide their physicochemical properties. Different physicochemical properties influence their application potential. Rhamnolipids can be produced at both aerobic conditions and anaerobic conditions by Pseudomonas aeruginosa. This study aims to evaluate the oxygen effects on the rhamnolipids yield, structural composition, physicochemical properties and the rhl-genes expression in P. aeruginosa SG. Results will guide researchers to regulate microbial cells to synthesize rhamnolipids with different activity according to diverse application requirements. RESULTS:Quantitative real-time PCR analysis revealed that rhlAB genes were down-regulated under anaerobic conditions. Therefore, strain P. aeruginosa SG anaerobically produced less rhamnolipids (0.68 g/L) than that (11.65 g/L) under aerobic conditions when grown in media containing glycerol and nitrate. HPLC-MS analysis showed that aerobically produced rhamnolipids mainly contained Rha-C8-C10, Rha-Rha-C10-C12:1 and Rha-Rha-C8-C10; anaerobically produced rhamnolipids mainly contained Rha-C10-C12 and Rha-C10-C10. Anaerobically produced rhamnolipids contained more mono-rhamnolipids (94.7%) than that (54.8%) in aerobically produced rhamnolipids. rhlC gene was also down-regulated under anaerobic conditions, catalyzing less mono-rhamnolipids to form di-rhamnolipids. Aerobically produced rhamnolipids decreased air-water surface tension (ST) from 72.2 to 27.9 mN/m with critical micelle concentration (CMC) of 60 mg/L; anaerobically produced rhamnolipids reduced ST to 33.1 mN/m with CMC of 80 mg/L. Anaerobically produced rhamnolipids emulsified crude oil with EI24 = 80.3%, and aerobically produced rhamnolipids emulsified crude oil with EI24 = 62.3%. Both two rhamnolipids products retained surface activity (ST < 35.0 mN/m) and emulsifying activity (EI24 > 60.0%) under temperatures (4-121 °C), pH values (4-10) and NaCl concentrations less than 90 g/L. CONCLUSIONS:Oxygen affected the rhl-genes expression in P. aeruginosa, thus altering the rhamnolipids yield, structural composition and physicochemical properties. Rhamnolipids produced at aerobic or anaerobic conditions was structurally distinct. Two rhamnolipids products had different application potential in diverse biotechnologies. Although both rhamnolipids products were thermo-stable and halo-tolerant, aerobically produced rhamnolipids possessed better surface activity, implying its well wetting activity and desorption property; anaerobically produced rhamnolipids exhibited better emulsifying activity, indicating its applicability for enhanced oil recovery and bioremediation of petroleum pollution.

Dataset Information

NOX4 Mediates Pseudomonas aeruginosa-Induced Nuclear Reactive Oxygen Species Generation and Chromatin Remodeling in Lung Epithelium.

Publications

NOX4 Mediates <i>Pseudomonas aeruginosa</i>-Induced Nuclear Reactive Oxygen Species Generation and Chromatin Remodeling in Lung Epithelium.

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