Early induction of uncoupling protein-2 in pulmonary macrophages in hyperoxia-associated lung injury

Steer, James H.; Mann, Tracy S.; Lo, Susan; Inglis, Julia J.; Yap, Huey S; Henry, Peter J.; Joyce, David A.

doi:10.3109/08958378.2013.810679

Cited by 12 publications

(7 citation statements)

References 56 publications

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“…Thus, this family of proteins protects against oxidative stress (Patti and Corvera, 2010; Echtay et al, 2002; Andrews et al, 2008; Jastroch et al, 2010; Krauss et al, 2005). A study by Steer, Mann (Steer et al, 2013) showed a significant induction of Ucp2 in murine pulmonary alveolar macrophages following exposure to high concentrations of oxygen. Particularly, this increment in protein levels of Ucp2 occurs in response to a rise in mitochondrial ROS production.…”

Section: Discussionmentioning

confidence: 99%

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

Pirela

Miousse

et al. 2016

NanoImpact

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Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use “real world” printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects.

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Section: Discussionmentioning

confidence: 99%

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

Pirela

Miousse

et al. 2016

NanoImpact

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“…Treatment with a mitochondria‐specific antioxidant, mitoTEMPO, during early post‐natal hyperoxia protected against compromised alveolarization (Datta et al , ), which suggests that targeted antioxidant therapy could be used to prevent or treat BPD. Hyperoxic exposure induces UCP2 expression in pulmonary macrophages and enhanced UCP3 levels in skeletal muscles in mice (Flandin et al , ; Steer et al , ), which may be compensatory responses to increased oxidative stress and mtROS. Further studies are required to determine the role of UCP in the development of BPD using genetic manipulation approaches.…”

Section: Mitochondrial Dysfunction In Chronic Lung Diseasesmentioning

confidence: 99%

Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases

Yao

2016

British J Pharmacology

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Mitochondria are dynamic organelles, which couple the various cellular processes that regulate metabolism, cell proliferation and survival. Environmental stress can cause mitochondrial dysfunction and dynamic changes including reduced mitochondrial biogenesis, oxidative phosphorylation and ATP production, as well as mitophagy impairment, which leads to increased ROS, inflammatory responses and cellular senescence. Oxidative stress, inflammation and cellular senescence all have important roles in the pathogenesis of chronic lung diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and bronchopulmonary dysplasia. In this review, we discuss the current state on how mitochondrial dysfunction affects inflammatory responses and cellular senescence, the mechanisms of mitochondrial dysfunction underlying the pathogenesis of chronic lung diseases and the potential of mitochondrial transfer and replacement as treatments for these diseases. AbbreviationsAMPK, AMP-activated protein kinase; α-SMA, α-smooth muscle actin; BPD, bronchopulmonary dysplasia; COPD, chronic obstructive pulmonary disease; DRP1, DNM1L, dynamin 1-like; Δψm, mitochondrial membrane potential; ETC, electron transport chain; FIS1, fission 1; MDVs, mitochondria-derived vesicles; Mfn, mitofusin; MiDAS, mitochondrial dysfunctionassociated senescence; MPTP, mitochondrial permeability transition pore; mtDNA, mitochondrial DNA; mtROS, mitochondrial ROS; O 2 .À , superoxide anion; OPA1, optic atrophy 1; PINK1, PTEN-induced putative kinase 1; SASP, senescenceassociated secretory phenotype; UCP, mitochondrial uncoupling protein

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“…Both 60-min bursts of hyperbaric oxygen and three-hour treatments with high-flow nasal cannula were shown to be efficacious, increasing cerebral blood flow and decreasing lactate levels with no sign of pulmonary or cerebral damage in patients with severe TBI [ 83 ]. Murine hyperoxia has been shown to induce UCP2 within 60 min, perhaps in response to the sudden increase in ROS production, suggesting a mechanism for this protection in which UCP2 was not being transcribed anew but that existing UCP2 mRNA and glutathione-coupled UCP2 were being mobilized; indeed, UCP2 protein level was found to increase with a corresponding decrease in ΔΨ m while the amount of UCP2 mRNA did not change [ 84 ]. This result extends specifically to toxicity mediated by hyperactivity associated with seizure in a murine model and is postulated to be at the core of the preconditioning phenomenon of cerebral vascular injury protection [ 32 ].…”

Section: Pathophysiology Of Ucp2mentioning

confidence: 99%

The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury

Normoyle

Kim

Farahvar

et al. 2015

Translational Neuroscience

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Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxidative stress, inflammation, and mitochondrial dysfunction. Mitochondria are critically regulated by uncoupling proteins (UCP), which allow protons to leak back into the matrix and thus reduce the mitochondrial membrane potential by dissipating the proton motive force. This uncoupling of oxidative phosphorylation from adenosine triphosphate (ATP) synthesis is potentially critical for protection against cellular injury as a result of TBI and stroke. A greater understanding of the underlying mechanism or mechanisms by which uncoupling protein-2 (UCP2) functions to maintain or optimize mitochondrial function, and the conditions which precipitate the failure of these mechanisms, would inform future research and treatment strategies. We posit that UCP2-mediated function underlies the physiological response to neuronal stress associated with traumatic and ischemic injury and that clinical development of UCP2-targeted treatment would significantly impact these patient populations. With a focus on clinical relevance in TBI, we synthesize current knowledge concerning UCP2 and its potential neuroprotective role and apply this body of knowledge to current and potential treatment modalities.

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Early induction of uncoupling protein-2 in pulmonary macrophages in hyperoxia-associated lung injury

Cited by 12 publications

References 56 publications

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases

The emerging neuroprotective role of mitochondrial uncoupling protein-2 in traumatic brain injury

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