NiONPs-induced alteration in calcium signaling and mitochondrial function in pulmonary artery endothelial cells involves oxidative stress and TRPV4 channels disruption

Abstract

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NiONP-Induced Oxidative Stress and Mitochondrial Impairment in an In Vitro Pulmonary Vascular Cell Model Mimicking Endothelial Dysfunction

“…In addition, we showed that NiONP exposure significantly increased global ROS and mitochondrial O 2 − production as compared to control cells. These results are in line with previously published data regarding NiONP exposure [24]. However, in cells exposed to NiONPs under pathological conditions, the increase in ROS and mitochondrial O 2 − production was greater than in HPAEC under physiological conditions.…”

“…Prior to use, stock suspensions were vortexed, sonicated at 3 × 30 s (Vibracell 75186, 130 W, 56-60 Hz), and diluted in ECGM extemporaneously at appropriate concentrations (0.5-5 µg/cm 2 ). The NiONPs were previously characterized by Germande et al, 2022 [24]. The hydrodynamic size distribution of NiONPs suspended in ECGM was determined at a concentration of 5 µg/cm 2 by dynamic light scattering (DLS) using a VASCO particle-size analyzer from Cordouan Technologies ® (Pessac, France).…”

“…Supernatants or cells were then collected to perform the experiments. The NiONPsworking concentrations for all experiments (for which the rate of mortality was under 30%) were all determined previously with the WST-1 assay test [24].…”

“…Furthermore, we previously demonstrated, in an in vitro study of EC, that NiONPs trigger significant oxidative stress. This was shown through an overproduction of reactive oxygen species (ROS) associated with a pro-inflammatory response, mitochondrial dysfunction, and calcium signaling alterations [24], all critical events involved in the pathophysiology of cardiovascular diseases such as pulmonary hypertension (PH) [25,26]. Moreover, our findings suggest that NiONPs interact with mechanosensitive ion channel TRPV4 (transient receptor potential vanilloid 4), which is expressed in vascular cells and is also involved in the remodeling of pulmonary arteries, a major feature of PH [27,28].…”

Inhibition of TRPA1 Ameliorates Periodontitis by Reducing Periodontal Ligament Cell Oxidative Stress and Apoptosis via PERK/eIF2α/ATF-4/CHOP Signal Pathway

“…Ca 2+ is a versatile and ubiquitous second messengers, and Ca 2+ changes play an interactional role in multiple biological processes [58]. Cytosolic Ca 2+ increase is always related with increased total ROS levels, cell apoptosis, energy metabolism dysfunction, ER stress, and mitochondrial dysfunction, and these processes will interactively further induce cytosolic Ca 2+ increase via regulating Ca 2+ gate by promoting the Ca 2+ leaking from the plasma membrane or ER [59,60]. Consistent with previous studies, we found increasing intracellular Ca 2+ concentration induced by TRPA1 activation in inflammation in this study, which is in accordance with high levels of OS markers, apoptosis, ER stress, and mitochondrial dysfunction and with TRPA1 inhibitor, and the above cell functions significantly decreased combined with decreased intracellular Ca 2+ concentration.…”