Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease

Boukhenouna, Samia; Wilson, Mark A.; Bahmed, Karim; Kośmider, Beata

doi:10.1155/2018/5730395

Cited by 191 publications

(123 citation statements)

References 85 publications

(96 reference statements)

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“…Oxidative stress caused by reactive oxygen species, a group of oxygen-based reactive molecules produced by ATO activated the NADPH-oxidase system, resulting in the disruption of mitochondrial membrane potential and subsequent apoptosis [27][28][29]. As published previously, the mRNA expression of NCF2/P67PHOX and GPPHOX91 were substantially higher in the presence of TG2 compared to NB4 TG2-KD and TG2-KO cells.…”

Section: Discussionsupporting

confidence: 61%

Benefits of Combined All-Trans Retinoic Acid and Arsenic Trioxide Treatment of Acute Promyelocytic Leukemia Cells and Further Enhancement by Inhibition of Atypically Expressed Transglutaminase 2

Jambrovics

Uray

Keillor

et al. 2020

Cancers

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Randomized trials in acute promyelocytic leukemia patients have shown that treatment with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) is superior in efficacy to monotherapy, with significantly decreased mortality. So far, there are little data available to explain the success of the ATRA and ATO combination treatment in molecular terms. We showed that ATRA-and ATO-treated cells had the same capacity for superoxide production, which was reduced by two-thirds in the combined treatment. Secreted inflammatory biomarkers (monocyte chemoattractant protein-1 [MCP-1], interleukin-1 beta [IL-1β] and tumor necrosis factor-α [TNF-α]) were significantly decreased and were further reduced in a transglutaminase 2 (TG2) expression-dependent manner. The amount of secreted TNF-α in the supernatant of NB4 TG2 knockout cells was close to 50 times lower than in ATRA-treated differentiated wild-type NB4 cells. The irreversible inhibitor of TG2 NC9 not only decreased reactive oxygen species production 28-fold, but decreased the concentration of MCP-1, IL-1β and TNF-α 8-, 15-and 61-fold, respectively in the combined ATRA + ATO-treated wild-type NB4 cell culture. We propose that atypical expression of TG2 leads to the generation of inflammation, which thereby serves as a potential target for the prevention of differentiation syndrome.(ATRA) both activates the PML-RARα chimera protein and initiates its proteolysis, resulting in the differentiation of APL leukemic cells [1][2][3].In the 2000s, arsenic trioxide (As 2 O 3 /ATO) was approved by the Food and Drug Administration (US FDA) to treat APL. Clinical data have shown that ATO, either as a single agent or combined with ATRA, can improve the outcomes in newly diagnosed and relapsed APL, compared to ATRA treatment alone [4][5][6].When combined with ATRA and chemotherapy, ATO can induce complete remission of APL patients, with a five-year overall survival rate up to 90% [5]. At the molecular level, ATO exhibits cytotoxic effects in a concentration-dependent manner, while at lower concentrations (< 0.5 µM), ATO can induce partial differentiation and at higher concentrations (> 0.5 µM), it initiates apoptosis of APL cells. Some of the signal transduction pathways and transactivations of transcription factors involved are arsenic-induced and redox-sensitive. These include the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1/2 (ERK1/2), stress-activated protein kinase/Jun-N terminal protein kinases (SAPK/JNK), the apoptosis signal-regulating kinase 1/thioredoxin (ASK1/TRX) system, the AKT-mTOR pathway, transcription factor AP-1 and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [7]. Although both ATO and ATRA prime the PML-RARα oncoprotein for proteolysis, only ATO is effective as a monotherapy, through the elimination of residual leukemia-initiating cells. The major limitation to ATO treatment is coagulopathy, which is one of the major causes of early death in APL, driven by procoagulant and fibrino...

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Section: Discussionsupporting

confidence: 61%

Benefits of Combined All-Trans Retinoic Acid and Arsenic Trioxide Treatment of Acute Promyelocytic Leukemia Cells and Further Enhancement by Inhibition of Atypically Expressed Transglutaminase 2

Jambrovics

Uray

Keillor

et al. 2020

Cancers

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“…Indeed, we identified increased baseline respiration in AMs of COPD patients ( Figure 5I), which reflects an elevated energy demand. We also found a significant increase in proton leakage in AMs of COPD patients, which is indicative for increased ROS production in COPD (Boukhenouna et al, 2018;Cheng et al, 2017;McGuinness and Sapey, 2017) and mitochondrial dysfunction (Eapen et al, 2019;Hoffmann et al, 2019;Ng Kee Kwong et al, 2017).…”

Section: Copd Leads To Major Changes In Most Am States 12supporting

confidence: 52%

Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary disease

Baßler

Fujii

Kapellos

et al. 2020

Preprint

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Despite the epidemics of chronic obstructive pulmonary disease (COPD), the cellular and molecular mechanisms of this disease are far from being understood. Here, we characterize and classify the cellular composition within the alveolar space and peripheral blood of COPD patients and control donors using a clinically applicable single-cell RNA-seq technology corroborated by advanced computational approaches for: machine learning-based cell-type classification, identification of differentially expressed genes, prediction of metabolic changes, and modeling of cellular trajectories within a patient cohort. These high-resolution approaches revealed: massive transcriptional plasticity of macrophages in the alveolar space with increased levels of invading and proliferating cells, loss of MHC expression, reduced cellular motility, altered lipid metabolism, and a metabolic shift reminiscent of mitochondrial dysfunction in COPD patients. Collectively, single-cell omics of multi-tissue samples was used to build the first cellular and molecular framework for COPD pathophysiology as a prerequisite to develop molecular biomarkers and causal therapies against this deadly disease.

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“…Oxidative stress often occurs in the course of unpredictable events that mainly target individual cells, such as inflammation, irradiation or poisoning, for example with cigarette smoke (Boukhenouna et al. ; Chen et al. ; Citrin & Mitchell, ).…”

Section: Reactive Oxygen Species Needed and Dangerousmentioning

confidence: 99%

“…The nature of oxidative stress includes unspecific oxidation of intracellular molecules, with potentially detrimental effects on cell function and survival (Misra, Sarwat, Bhakuni, Tuteja, & Tuteja, 2009). Oxidative stress often occurs in the course of unpredictable events that mainly target individual cells, such as inflammation, irradiation or poisoning, for example with cigarette smoke (Boukhenouna et al 2018;Chen et al 2018;Citrin & Mitchell, 2017). Although oxidative stress appears to be an accident, this is unlikely to be true.…”

Section: Reactive Oxygen Species Needed and Dangerousmentioning

confidence: 99%

NADPH oxidase‐derived reactive oxygen species: Dosis facit venenum

Schröder

2019

Experimental Physiology

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New Findings What is the topic of this review? Within this review, the role of reactive oxygen species in cellular homeostasis, physiology and pathophysiology is discussed. What advances does it highlight? The review provides new concepts of how reactive oxygen species influence gene expression, energy consumption and other aspects of the life of a cell. Furthermore, a model is provided to illustrate how reactive oxygen species elicit specific oxidation of target molecules. Abstract Reactive oxygen species (ROS) have a long history of bad reputation. They are needed and effective in host defense, but on the contrary may induce situations of oxidative stress. Besides that, within recent years several soft functions (functions that may occur and are not directly connected to an effect, but may influence signaling in an indirect manner) of NADPH oxidases have been discovered, which are slowly eroding the image of the solely dangerous ROS. NADPH oxidase‐derived ROS serve to ease or enable signal transduction and to maintain homeostasis. However, there is still an enormous lag in the knowledge concerning target proteins and how ROS can elicit specific signalling in different cells and tissues. The present review summarizes some important functions of Nox2 and Nox4. Furthermore, although highly speculative, a model is provided of how those NADPH oxidases might be able to oxidize target proteins in a specific way. Many concepts mentioned in this review represent my personal view and are supported only in part by published studies.

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Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease

Cited by 191 publications

References 85 publications

Benefits of Combined All-Trans Retinoic Acid and Arsenic Trioxide Treatment of Acute Promyelocytic Leukemia Cells and Further Enhancement by Inhibition of Atypically Expressed Transglutaminase 2

Benefits of Combined All-Trans Retinoic Acid and Arsenic Trioxide Treatment of Acute Promyelocytic Leukemia Cells and Further Enhancement by Inhibition of Atypically Expressed Transglutaminase 2

Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary disease

NADPH oxidase‐derived reactive oxygen species: Dosis facit venenum

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