Ozone induces BEL7402 cell apoptosis by increasing reactive oxygen species production and activating JNK

Tang, Shuiying; Xu, Bihong; Li, Jincheng; Zhong, Meifeng; Hong, Ziyang; Zhao, Wei; Zeng, Tao; He, Xiaofeng

doi:10.21037/atm-21-3233

Cited by 2 publications

(1 citation statement)

References 37 publications

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“…Eventually, both pathways converge into the signaling pathway for the execution phase, triggered by caspases-8, -9, and -10, and activate executioner caspases-3 and -6, and finally, endonucleases that disassemble the nucleus eliminating DNA, RNA, and proteases, which degrade actin and tubulin in the cytoskeleton. Ultimately, cytoplasmic vesicles disassemble the damaged cell into apoptotic bodies [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Exposure to Ozone Downregulates Bcl-2 and Increases Executing Caspases-3 and -8 in the Hippocampus, Frontal Cortex, and Cerebellum of Rats

Rodríguez-Quintero,

Rubio-Osornio,

Uribe

et al. 2024

Cureus

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Introduction Ozone (O3) is one of the most prevalent atmospheric pollutants, arising from a photochemical reaction between volatile organic compounds (VOC), nitrogen oxides (NOx), and sunlight. O3 triggers oxidative stress, resulting in lipid oxidation, inflammation, alterations in metabolic and cellular signaling, and potentially initiating cell death in vulnerable brain regions. Inflammation and oxidative stress are recognized for their ability to induce cell death, primarily through the apoptosis pathway, involving various proteins that participate in this process via two pathways: intrinsic and extrinsic. Objective This study aims to identify the expression of pro-apoptotic proteins and Bcl-2 in the frontal cortex, cerebellum, and hippocampus of rats exposed to O3 acutely. Methods Two groups of 20 Wistar rodents (250-300 g) were established. The control group (n=10) was exposed to unrestricted polluted air for 12 hours, while the experimental group (n=10) was exposed to 1 ppm of O3. After exposure, the animals were sacrificed for immunofluorescence and Western blot analysis. Using a t-test, the arbitrary units of pro-apoptotic proteins and Bcl-2 were compared between the two groups. Results Significant increases in caspase-8 and caspase-3 activation were found in the O3-exposed group compared to the control group, specifically in the frontal cortex, cerebellum, and hippocampus. Additionally, notable changes in Bcl-2 expression were observed in these brain regions. The TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay further indicated significant differences in immunopositivity between the groups in the same areas. However, intrinsic apoptotic proteins such as Bax, VDAC1, and cytochrome-c did not show significant differences between the groups within these structures. Western blot analyses aligned with the immunofluorescence results, showing statistically significant concentrations of caspase-8 in the cerebellum, caspase-3 in the hippocampus, and Bcl-2 in the frontal cortex in the O3 exposed group. Conversely, proteins like Bax, cytochrome-c, and VDAC1 did not exhibit significant differences in all analyzed structures. Conclusions This study demonstrates that acute exposure to 1 ppm of ozone can trigger neuronal apoptosis in the frontal cortex, hippocampus, and cerebellum of rats, primarily through the activation of the extrinsic apoptosis pathway via caspase-8 and caspase-3. Additionally, it causes a reduction in Bcl-2 expression, an essential antiapoptotic protein. Despite not observing the activation of intrinsic pathway proteins like BAX, VDAC, or cytochrome-c, the study suggests that chronic O3 exposure might promote cell death by activating this pathway, requiring further long-term research.

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Section: Introductionmentioning

confidence: 99%

Exposure to Ozone Downregulates Bcl-2 and Increases Executing Caspases-3 and -8 in the Hippocampus, Frontal Cortex, and Cerebellum of Rats

Rodríguez-Quintero,

Rubio-Osornio,

Uribe

et al. 2024

Cureus

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Low-Dose Ozone as a Eustress Inducer: Experimental Evidence of the Molecular Mechanisms Accounting for Its Therapeutic Action

Malatesta,

Tabaracci,

Pellicciari

2024

IJMS

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Ozone (O3) is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O3 dates back to the beginning of 20th century and is currently based on the application of low doses, inducing moderate oxidative stress that stimulates the antioxidant cellular defences without causing cell damage. In recent decades, experimental investigations allowed the establishment of some basic mechanisms accounting for the therapeutic effects of eustress-inducing low-dose O3. In this review, special attention was given to the impact of O3 administration on the cell oxidant–antioxidant status, O3 anti-inflammatory and analgesic properties, efficacy in improving tissue regeneration, and potential anticancer action. Low O3 concentrations proved to drive the cell antioxidant response mainly by activating nuclear factor erythroid 2-related factor 2. The anti-inflammatory effect relies on the downregulation of pro-inflammatory factors and the modulation of cytokine secretion. The painkilling action is related to anti-inflammatory processes, inhibition of apoptosis and autophagy, and modulation of pain receptors. The regenerative potential depends on antioxidant, anti-inflammatory, anti-apoptotic, and pro-proliferative capabilities, as well as fibroblast activation. Finally, the anticancer potential is based on oxidant and anti-inflammatory properties, as well as the inhibition of cell proliferation, invasion, and migration and the induction of apoptosis.

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Ozone induces BEL7402 cell apoptosis by increasing reactive oxygen species production and activating JNK

Cited by 2 publications

References 37 publications

Exposure to Ozone Downregulates Bcl-2 and Increases Executing Caspases-3 and -8 in the Hippocampus, Frontal Cortex, and Cerebellum of Rats

Exposure to Ozone Downregulates Bcl-2 and Increases Executing Caspases-3 and -8 in the Hippocampus, Frontal Cortex, and Cerebellum of Rats

Low-Dose Ozone as a Eustress Inducer: Experimental Evidence of the Molecular Mechanisms Accounting for Its Therapeutic Action

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