No abstract

Exposure to ambient fine particulate matter (PM2.5) increases the risk of respiratory disease. Although previous mitochondrial research has provided new information about PM toxicity in the lung, the exact mechanism of PM2.5-mediated structural and functional damage of lung mitochondria remains unclear. In this study, changes in lung mitochondrial morphology, expression of mitochondrial fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM2.5 at different dosages were investigated. Also, the release of reactive oxygen species (ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed to PM2.5 was examined by luminol-dependent chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung and induced pathological damage, particularly causing abnormal alterations of mitochondrial structure, including mitochondrial swelling and cristae disorder or even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5 significantly affected the expression of specific mitochondrial fission/fusion markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM2.5 inhibited Mn superoxide dismutase (MnSOD), Na(+)K(+)-ATPase, and Ca(2+)-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM2.5 induced rat AMs to produce ROS, which was inhibited by about 84.1% by diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is suggested that the pathological injury observed in rat lung exposed to PM2.5 is associated with mitochondrial fusion-fission dysfunction, ROS generation, mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to lung mitochondria may be one of the important mechanisms by which PM2.5 induces lung injury, contributing to respiratory diseases.

Fine particulate matter (PM2.5) exposure is associated with morbidity and mortality induced by respiratory diseases and increases the lung cancer risk. However, the mechanisms therein involved are not yet fully clarified. In this study, the PM2.5 suspensions at different dosages (0.375, 1.5, 6.0, and 24.0 mg/kg body weight) were respectively given to rats by the intratracheal instillation. The results showed that PM2.5 exposure induced inflammatory cell infiltration and hyperemia in the lung tissues and increased the inflammatory cell numbers in bronchoalveolar lavage fluid. Furthermore, PM2.5 significantly elevated the levels of pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, and intercellular adhesion molecule 1 (ICAM-1) and the expression of c-fos and c-jun in rat lungs exposed to higher dose of PM2.5. These changes were accompanied by decreases of activities of superoxide dismutase and increases of levels of malondialdehyde, inducible nitric oxide synthase, nitric oxide, cytochrome P450s, and glutathione S-transferase. The results implicated that acute exposure to PM2.5 induced pathologically pulmonary changes, unchained inflammatory and oxidative stress processes, activated metabolic enzyme activity, and enhanced proto-oncogene expression, which might be one of the possible mechanisms by which PM2.5 pollution induces lung injury and may be the important determinants for the susceptibility to respiratory diseases.

No abstract

Substituted para -phenylenediamine (PPD) antioxidants have been extensively used to retard oxidative degradation of tire rubber and were found to pervade multiple environmental compartments. However, there is a paucity of research on the environmental occurrences of their transformation products. In this study, we revealed the co-occurrence of six PPD-derived quinones (PPD-Qs) along with eight PPDs in fine particulate matter (PM 2.5 ) from two Chinese megacities, in which N , N ′-bis(1,4-dimethylpentyl)- p -phenylenediamine quinone (77PD-Q) was identified and quantified for the first time. Prevalent occurrences of these emerging PPD-Qs were found in Taiyuan (5.59–8480 pg/m 3 ) and Guangzhou (3.61–4490 pg/m 3 ). Significantly higher levels of PPDs/PPD-Qs were observed at a roadside site, implying the possible contribution of vehicle emissions. Correlation analysis implied potential consistencies in the fate of these PPD-Qs and suggested that most of them were originated from the transformation of their parent PPDs. For different subpopulation groups under different exposure scenarios, the estimated daily intakes of PPD-Qs (0.16–1.25 ng kg bw –1 day –1 ) were comparable to those of their parent PPDs (0.19–1.41 ng kg bw –1 day –1 ), suggesting an important but overlooked exposure caused by novel PPD-Qs. Given the prolonged exposure of these antioxidants and their quinone derivatives to traffic-relevant occupations, further investigations on their toxicological and epidemiological effects are necessary.

No abstract

Cadmium (Cd) is an environmental pollutant and has been found to pose a potential threat to human health. Isoquercitrin (IQ) is one of the most important flavonoids and has been demonstrated to exhibit potent antioxidant effects on plants and yeast cells. However, only few studies have investigated the antioxidative activities of reactive oxygen species (ROS) and the nitrite scavenging activities of IQ against Cd-induced oxidation in mouse. The present work was to investigate the ROS and nitrite-scavenging activities of IQ in vitro as well as its preventive effects against lipid peroxidation and protein oxidative damage in liver and kidney of mouse induced by Cd(²+) using spectrophotometry. Our results showed that IQ possesses scavenging abilities for superoxide anion, hydroxyl radical and nitrite. Such scavenging capacities increase with the concentration of IQ. Moreover, cadmium chloride (CdCl₂ (2.5 mg/kg body weight, i.p. CdCl₂) significantly inhibited the activities of superoxide dismutase and catalase and raised the levels of malondialdehyde, nitric oxide, protein carbonyl, and the coefficients of DNA-protein crosslinks in livers and/or kidneys of mice. IQ attenuated the Cd(²+)-induced biochemical alterations in the livers and/or kidneys of mice, indicating that the formation of ROS and nitrite is possibly reduced. Our work demonstrates that IQ possesses ROS and nitrite-scavenging capacities and plays a significant role in combating Cd(²+)-induced toxicity in animals.

Aim: Oxidative stress induced by free fatty acids (FFA) contributes to metabolic syndrome-associated development of cardiovascular diseases, yet molecular mechanisms remain poorly understood. This study aimed at establishing whether phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and its subcellular location play a role in FFA-induced endothelial oxidative stress. Results: Exposing human endothelial cells (ECs) with FFA activated mammalian target of rapamycin (mTOR)/S6K pathway, and upon activation, S6K directly phosphorylated PTEN at S380. Phosphorylation of PTEN increased its interaction with its deubiquitinase USP7 in the nucleus, leading to PTEN deubiquitination and nuclear export. The reduction of PTEN in the nucleus, in turn, decreased p53 acetylation and transcription, reduced the expression of the p53 target gene glutathione peroxidase-1 (GPX1), resulting in reactive oxygen species (ROS) accumulation and endothelial damage. Finally, C57BL/6J mice fed with high-fat atherogenic diet (HFAD) showed PTEN nuclear export, decreased p53 and GPX1 protein expressions, elevated levels of ROS, and significant lesions in aortas. Importantly, inhibition of mTOR or S6K effectively blocked these effects, suggesting that mTOR/S6K pathway mediates HFAD-induced oxidative stress and vascular damage via PTEN/p53/GPX1 inhibition in vivo. Innovation: Our study demonstrated for the first time that S6K directly phosphorylated PTEN at S380 under high FFA conditions, and this phosphorylation mediated FFA-induced endothelial oxidative stress. Furthermore, we showed that S380 phosphorylation affected PTEN monoubiquitination and nuclear localization, providing the first example of coordinated regulation of PTEN nuclear localization via phosphorylation and ubiquitination. Conclusion: Our studies provide a novel mechanism by which hyperlipidemia causes vascular oxidative damage through the phosphorylation of PTEN, blocking of PTEN nuclear function, and inhibition of p53/GPX1 activity. Antioxid. Redox Signal. 20, 1382Signal. 20, -1395