Combustion Particle-Induced Changes in Calcium Homeostasis: A Contributing Factor to Vascular Disease?

Holme, Jørn A.; Brinchmann, Bendik Christian; Ferrec, Eric Le; Lagadic‐Gossmann, Dominique; Øvrevik, Johan

doi:10.1007/s12012-019-09518-9

Cited by 20 publications

(18 citation statements)

References 149 publications

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“…Unfortunately, we are not able to identify speci c ROS species generated upon CBNP exposure in A459 cells, however, both antioxidants NAC and Trolox considerably inhibited the ROS level thus suggesting that the increased ROS levels are an effect of different ROS species generated and are not dependent on an individual chemical species only. Other than ROS generation, CBNP exposure in A549 cells also exhibited a transient increase in calcium levels as also observed in other studies [11]. A slight disturbance in calcium homeostasis was observed already after three hours of exposure which increased consistently over 6 h which remain consistent even after 24 h exposure.…”

Section: Disturbance In Calcium Homeostasis and The Generation Of Oxisupporting

confidence: 86%

“…High ROS levels thus generated are known further to cause severe cell damage which ultimately leads to cell death, however, often this switch is mediated by calcium signaling [9]. Disturbance in calcium homeostasis upon nanoparticle exposure has been reported in many studies [10,11] but a mutual interplay of ROS and calcium ions upon nanoparticle exposure has hardly been explored [12]. Increasing evidence suggests that interactions between calcium and ROS are necessary for signaling and proper functioning of cellular signaling networks [13,14,15].…”

Section: Introductionmentioning

confidence: 99%

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A New Perspective on Calmodulin Regulated Calcium and Ros Homeostasis Upon Carbon Black Nanoparticle Exposure

Verma

Pink

Schmitz‐Spanke

2020

Preprint

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BackgroundToxicological studies propose that exposure to carbon black nanoparticles induces organ injuries and inflammatory responses. Besides, current understanding of the molecular mechanisms implies that carbon black nanoparticles (CBNP) exposure induces the production of reactive oxygen species (ROS) causing inflammation, mitochondrial dysfunction, or disturbance in calcium homeostasis. However, the precise mechanisms whereby CBNP exert these effects in the lung are still not fully understood. To gain insight into the possible mechanism of CBNP exerted toxicity, human alveolar epithelial cells (A549) were exposed to different concentrations of CBNP and for different time points. The reaction of the cells was monitored by the systematic use of cell-based measurements of calcium and ROS, in the presence and absence of calcium (Ca2+) pump inhibitors/chelators and antioxidants. Followed by an in-depth PCR analysis of eighty-four oxidative stress related genes.ResultsThe measurements revealed, as compared to the control, that exposure to CBNP nanoparticles leads to the generation of high ROS levels as well as a disturbance in calcium homeostasis, which remained primarily unchanged even after 24 h of exposure. Nevertheless, in presence of antioxidants N-acetylcysteine (NAC) and Trolox, ROS formation was considerably reduced without affecting the intracellular calcium concentration. On the other hand, Ca2+ pump inhibitors/chelators, BAPTA (1,2-bis(o-amino phenoxy)ethane-N, N, N′, N′-tetraacetic acid) and verapamil not only decreased the Ca2+ overload but also further decreased the ROS formation, indicating its role in CBNP induced oxidative stress. Further, a PCR array analysis of A549 cells in presence and absence of the calmodulin (CaM) antagonist W7, indicated towards nine altered oxidative stress-related genes which further confirmed our cytotoxicity results. The results suggested that CBNP exposure elevates calcium ion concentration, which further contributes to oxidative stress, via the calcium-binding protein CaM. Its inhibition with W7 leads to downregulation in gene expression of nine oxidative stress-related genes, which otherwise, as compared to control, show increased gene expression.ConclusionsThe results of the study thus confirm that exposure of lung epithelial cells to CBNP leads to oxidative stress, however, the oxidative stress itself is a result of a disturbance in both calcium and ROS homeostasis and should be considered while searching for a new strategy for prevention of CBNP - induced lung toxicity.

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Section: Disturbance In Calcium Homeostasis and The Generation Of Oxisupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

A New Perspective on Calmodulin Regulated Calcium and Ros Homeostasis Upon Carbon Black Nanoparticle Exposure

Verma

Pink

Schmitz‐Spanke

2020

Preprint

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“…Mitochondria have a critical role in the local Ca 2+ control. Alteration in calcium signaling mechanisms by the CFDNPs may thus be of key myocardial and vascular importance (Holme et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Combustion- and friction-derived magnetic air pollution nanoparticles in human hearts

Calderón‐Garcidueñas

González-Maciel

Mukherjee

et al. 2019

Environmental Research

142

115

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“…There is an extensive crosstalk between AhR and the proinflammatory transcription factor NF-κB [108], and AhR may also be directly involved in the transcriptional regulation of proinflammatory genes [109,110,111,112,113,114]. AhR and PAHs also appear to play a central role in CVD, as reviewed elsewhere [115,116,117], providing a potential link between PM exposure and adverse effects. These are other possible components and effects not picked-up by acellular assays for OP.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

Øvrevik

2019

IJMS

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Background and Objectives: The oxidative potential (OP) of particulate matter (PM) in cell-free/abiotic systems have been suggested as a possible measure of their biological reactivity and a relevant exposure metric for ambient air PM in epidemiological studies. The present review examined whether the OP of particles correlate with their biological effects, to determine the relevance of these cell-free assays as predictors of particle toxicity. Methods: PubMed, Google Scholar and Web of Science databases were searched to identify relevant studies published up to May 2019. The main inclusion criteria used for the selection of studies were that they should contain (1) multiple PM types or samples, (2) assessment of oxidative potential in cell-free systems and (3) assessment of biological effects in cells, animals or humans. Results: In total, 50 independent studies were identified assessing both OP and biological effects of ambient air PM or combustion particles such as diesel exhaust and wood smoke particles: 32 in vitro or in vivo studies exploring effects in cells or animals, and 18 clinical or epidemiological studies exploring effects in humans. Of these, 29 studies assessed the association between OP and biological effects by statistical analysis: 10 studies reported that at least one OP measure was statistically significantly associated with all endpoints examined, 12 studies reported that at least one OP measure was significantly associated with at least one effect outcome, while seven studies reported no significant correlation/association between any OP measures and any biological effects. The overall assessment revealed considerable variability in reported association between individual OP assays and specific outcomes, but evidence of positive association between intracellular ROS, oxidative damage and antioxidant response in vitro, and between OP assessed by the dithiothreitol (DDT) assay and asthma/wheeze in humans. There was little support for consistent association between OP and any other outcome assessed, either due to repeated lack of statistical association, variability in reported findings or limited numbers of available studies. Conclusions: Current assays for OP in cell-free/abiotic systems appear to have limited value in predicting PM toxicity. Clarifying the underlying causes may be important for further advancement in the field.

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Combustion Particle-Induced Changes in Calcium Homeostasis: A Contributing Factor to Vascular Disease?

Cited by 20 publications

References 149 publications

A New Perspective on Calmodulin Regulated Calcium and Ros Homeostasis Upon Carbon Black Nanoparticle Exposure

A New Perspective on Calmodulin Regulated Calcium and Ros Homeostasis Upon Carbon Black Nanoparticle Exposure

Combustion- and friction-derived magnetic air pollution nanoparticles in human hearts

Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

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