Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation

Li, Rongsong; Ning, Zhi; Cui, Jeffrey; Khalsa, Bhavraj; Ai, Lisong; Takabe, Wakako; Beebe, Tyler; Majumdar, Rohit; Sioutas, Constantinos; Hsiai, Tzung K.

doi:10.1016/j.freeradbiomed.2008.11.025

Cited by 87 publications

(80 citation statements)

References 51 publications

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“…Protein concentration was measured using the Bio-Rad DC assay and 50 lg of protein was loaded for Western blotting essentially as previously described (53). Antibodies against autophagyassociated genes were purchased from Abcam for LC3 and from Boster Biological Technologies for p62.…”

Section: Western Blot Analysesmentioning

confidence: 99%

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Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis

Jen

et al. 2015

Antioxidants & Redox Signaling

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Aim: Temporal and spatial variations in shear stress are intimately linked with vascular metabolic effects. Autophagy is tightly regulated in intracellular bulk degradation/recycling system for maintaining cellular homeostasis. We postulated that disturbed flow modulates autophagy with an implication in mitochondrial superoxide (mtO 2 -) production. Results: In the disturbed flow or oscillatory shear stress (OSS)-exposed aortic arch, we observed prominent staining of p62, a reverse marker of autophagic flux, whereas in the pulsatile shear stress (PSS)-exposed descending aorta, p62 was attenuated. OSS significantly increased (i) microtubuleassociated protein light chain 3 (LC3) II to I ratios in human aortic endothelial cells, (ii) autophagosome formation as quantified by green fluorescent protein (GFP)-LC3 dots per cell, and (iii) p62 protein levels, whereas manganese superoxide dismutase (MnSOD) overexpression by recombinant adenovirus, N-acetyl cysteine treatment, or c-Jun N-terminal kinase ( JNK) inhibition reduced OSS-mediated LC3-II/LC3-I ratios and mitochondrial DNA damage. Introducing bafilomycin to Earle's balanced salt solution or to OSS condition incrementally increased both LC3-II/LC3-I ratios and p62 levels, implicating impaired autophagic flux. In the OSS-exposed aortic arch, both anti-phospho-JNK and anti-8-hydroxy-2¢-deoxyguanosine (8-OHdG) staining for DNA damage were prominent, whereas in the PSS-exposed descending aorta, the staining was nearly absent. Knockdown of ATG5 with siRNA increased OSS-mediated mtO 2 -, whereas starvation or rapamycin-induced autophagy reduced OSS-mediated mtO 2 -, mitochondrial respiration, and complex II activity. Innovation: Disturbed flow-mediated oxidative stress and JNK activation induce autophagy. Conclusion: OSS impairs autophagic flux to interfere with mitochondrial homeostasis.

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Section: Western Blot Analysesmentioning

confidence: 99%

“…Parallel blots were performed with anti-b-tubulin (Millipore, Inc.) for loading normalization. Densitometry was performed to quantify blot bands as previously described (53).…”

Section: Western Blot Analysesmentioning

confidence: 99%

Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis

Jen

et al. 2015

Antioxidants & Redox Signaling

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“…While heavy-duty diesel vehicles constitute only a small fraction of the total fleet in California (CA) and the United States, diesel particulate mass contributes significantly to urban air pollution and has been associated with adverse health effects (EPA 2002;Li et al 2009). Standards for vehicle particulate matter (PM) emissions in the US are presently based on mass, while particle number emissions are not regulated directly.…”

Section: Introductionmentioning

confidence: 99%

Nature of Sub-23-nm Particles Downstream of the European Particle Measurement Programme (PMP)-Compliant System: A Real-Time Data Perspective

Zheng

Durbin

Karavalakis

et al. 2012

Aerosol Science and Technology

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This study provides an evaluation of the nature of sub-23-nm particles downstream of the European Particulate Measurement Programme (PMP) methodology, with prescribed cycles and on-road flow-of-traffic driving conditions. Particle number concentrations and size distributions were measured using two PMP measurement systems running simultaneously. For this analysis, the focus is on the real-time results from multiple instruments. The results revealed that a significant fraction of particles downstream of both PMP systems for all tested cycles were below 11 nm. The fraction of sub-11-nm particles observed downstream of the PMP system decreased when the overall dilution ratio of one PMP system was increased from 300 to 1500, suggesting those sub-11-nm particles were formed through re-nucleation of semivolatile precursors. When the evaporation tube temperature was increased from 300• C to 500 • C, no difference in particle number concen- Address correspondence to Heejung S. Jung, Department of Mechanical Engineering, University of California, Riverside, A357 Bourns Hall, 900 University Avenue, Riverside, CA 92521, USA. E-mail: heejung@engr.ucr.edu trations was observed, suggesting that incomplete evaporation of semivolatile particles did not contribute to those sub-11-nm particles. Particle emissions were about one order of magnitude higher during flow-of-traffic driving along a highway with a steep grade than during the prescribed driving cycles. During the same flowof-traffic condition, a sudden jump in PMP operationally defined solid particle concentration was observed, while the accumulation mode particle concentrations in the constant volume sampling (CVS) tunnel measured by an engine exhaust particle sizer (EEPS) only showed a slight increase. This discrepancy was attributed to the extensive growth of the re-nucleated particles downstream of the PMP systems.

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“…As a control for in vitro experiments with resuspended nPM, fresh sterile filters were sham extracted. Aqueous nPM suspensions were pooled and frozen as a stock at -20°C, which retains chemical stability for ≥ 3 months (Li N et al 2003;Li R et al 2009). For in vitro experiments, nPM suspensions were diluted in culture medium, vortexed, and added directly to cultures.…”

Section: Methodsmentioning

confidence: 99%

“…Watersoluble organic carbon was assayed by a GE-Sievers liquid analyzer (GE-Sievers, Boulder, CO). Analytic details for nPMbound species are given by Li R et al (2009). Samples of the reaerosolized nPM were collected on parallel Teflon filters for electron paramagnetic resonance (EPR) analysis.…”

Section: Methodsmentioning

confidence: 99%

Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro

Morgan¹,

Davis²,

Iwata³

et al. 2015

Research

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Background: Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented. Objective: We evaluated rodent brain responses to urban nanoscale (< 200 nm) PM (nPM). Methods: Ambient nPM collected near an urban freeway was transferred to aqueous suspension and reaerosolized for 10-week inhalation exposure of mice or directly applied to rat brain cell cultures. Results: Free radicals were detected by electron paramagnetic resonance in the nPM 30 days after initial collection. Chronic inhalation of reaerosolized nPM altered selected neuronal and glial activities in mice. The neuronal glutamate receptor subunit (GluA1) was decreased in hippo campus, whereas glia were activated and inflammatory cytokines were induced [interleukin-1α (IL-1α), tumor necrosis factor-α (TNFα)] in cerebral cortex. Two in vitro models showed effects of nPM suspensions within 24-48 hr of exposure that involved glutamatergic functions. In hippocampal slice cultures, nPM increased the neurotoxicity of NMDA (N-methyl-d-aspartic acid), a glutamatergic agonist, which was in turn blocked by the NMDA antagonist AP5 [(2R)-amino-5-phosphonopentanoate]. In embryonic neuron cultures, nPM impaired neurite outgrowth, also blocked by AP5. Induction of IL-1α and TNFα in mixed glia cultures required higher nPM concentrations than did neuronal effects. Because conditioned media from nPM-exposed glia also impaired outgrowth of embryonic neurites, nPM can act indirectly, as well as directly, on neurons in vitro. Conclusions: nPM can affect embryonic and adult neurons through glutamatergic mechanisms. The interactions of nPM with glutamatergic neuronal functions suggest that cerebral ischemia, which involves glutamatergic excitotoxicity, could be exacerbated by nPM.

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Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation

Cited by 87 publications

References 51 publications

Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis

Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis

Nature of Sub-23-nm Particles Downstream of the European Particle Measurement Programme (PMP)-Compliant System: A Real-Time Data Perspective

Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro

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