Elimination of dysfunctional mitochondria through mitophagy suppresses benzo[a]pyrene-induced apoptosis

Das, Durgesh Nandini; Naik, Prajna Paramita; Mukhopadhyay, Subhadip; Panda, Prashanta Kumar; Sinha, Niharika; Meher, Biswa Ranjan; Bhutia, Sujit K.

doi:10.1016/j.freeradbiomed.2017.08.020

Cited by 62 publications

(32 citation statements)

References 34 publications

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“…Moreover, benzo[a]pyrene was shown to increase mitochondrial dysfunction and decrease the mitochondrial membrane potential, resulting in the depletion of ATP levels along with inhibition of the oxygen consumption rate in the human keratinocyte cell line (HACAT). In this study, it was shown that the removal of damaged mitochondria by mitophagy is reduced in AhR and CYP1B1 (an AhR target gene) knockdown but a direct link between AhR and mitophagy was not established (Das et al, 2017). In another study genetic ablation of the AhR resulted in reduced expression of Superoxide Dismutases (SODs) in fibroblasts.…”

Section: Ahr-mitochondria Crosstalkmentioning

confidence: 95%

The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor

et al. 2020

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Aging is the most important risk factor for the development of major life-threatening diseases such as cardiovascular disorders, cancer, and neurodegenerative disorders. The aging process is characterized by the accumulation of damage to intracellular macromolecules and it is concurrently shaped by genetic, environmental and nutritional factors. These factors influence the functionality of mitochondria, which play a central role in the aging process. Mitochondrial dysfunction is one of the hallmarks of aging and is associated with increased fluxes of ROS leading to damage of mitochondrial components, impaired metabolism of fatty acids, dysregulated glucose metabolism, and damage of adjacent organelles. Interestingly, many of the environmental (e.g., pollutants and other toxicants) and nutritional (e.g., flavonoids, carotenoids) factors influencing aging and mitochondrial function also directly or indirectly affect the activity of a highly conserved transcription factor, the Aryl hydrocarbon Receptor (AhR). Therefore, it is not surprising that many studies have already indicated a role of this versatile transcription factor in the aging process. We also recently found that the AhR promotes aging phenotypes across species. In this manuscript, we systematically review the existing literature on the contradictory studies indicating either pro-or anti-aging effects of the AhR and try to reconcile the seemingly conflicting data considering a possible dependency on the animal model, tissue, as well as level of AhR expression and activation. Moreover, given the crucial role of mitochondria in the aging process, we summarize the growing body of evidence pointing toward the influence of AhR on mitochondria, which can be of potential relevance for aging.

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Section: Ahr-mitochondria Crosstalkmentioning

confidence: 95%

The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor

et al. 2020

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“…Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that is activated by small molecules provided by the diet, microorganisms, metabolism, and pollutants . Upon ligand binding, AhR translocates from cytosol to the nucleus, leading to changes in target gene transcription (eg, cytochrome P450 cyp1a1, cyp1b1) and immunotoxicological effects .…”

Section: Introductionmentioning

confidence: 99%

Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)‐induced epithelial cytokine release through aryl hydrocarbon receptor in asthma

Wang

Liu

et al. 2019

Allergy

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Background Environmental pollutants, which coexist with allergens, have been associated with the exacerbation of asthma. However, the underlying molecular mechanisms remain elusive. We sought to determine whether benzo(a)pyrene (BaP) co‐exposure with dermatophagoides group 1 allergen (Der f 1) can potentiate Der f 1‐induced asthma and its underlying mechanisms. Methods The effect of BaP was investigated in Der f 1‐induced mouse model of asthma, including airway hyper‐responsiveness, allergic inflammation, and epithelial‐derived cytokines. The impact of BaP on Der f 1‐induced airway epithelial cell oxidative stress (ROS) and cytokine release was further analyzed. The role of aryl hydrocarbon receptor (AhR) signaling in BaP‐promoted Der f 1‐induced ROS, cytokine production, and allergic inflammation was also investigated. Results Compared with Der f 1, BaP co‐exposure with Der f 1 led to airway hyper‐responsiveness and increased lung inflammation in mouse model of asthma. Increased expression of TSLP, IL‐33, and IL‐25 was also found in the airways of these mice. Moreover, BaP co‐exposure with Der f 1 activated AhR signaling with increased expression of AhR and CYP1A1 and promoted airway epithelial ROS generation and TSLP and IL‐33, but not IL‐25, expression. Interestingly, AhR antagonist CH223191 or cells with AhR knockdown abrogated the increased expression of ROS, TSLP, and IL‐33. Furthermore, ROS inhibitor N‐acetyl‐L‐cysteine (NAC) also suppressed BaP co‐exposure‐induced expression of epithelial TSLP, IL‐33, and IL‐25. Finally, AhR antagonist CH223191 and NAC inhibited BaP co‐exposure with Der f 1‐induced lung inflammation. Conclusions Our findings suggest that BaP facilitates Der f 1‐induced epithelial cytokine release through the AhR‐ROS axis.

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“…Non-exhaustively, cadmium [97], arsenic [98], paraquat [99], bisphenol A [100], patulin [101] and TCDD [102,103], have been shown to differentially affect autophagy. Of particular interest here, two previous studies have also reported that B[a]P can modulate both autophagy [104] and mitophagy [105].…”

Section: -3-1-autophagy: a Key Cellular Process To Cope With Stressfmentioning

confidence: 81%

Disturbances in H+ dynamics during environmental carcinogenesis

et al. 2019

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Abbreviations: B[a]P: benzo[a]pyrene; GPCR: G-protein coupled receptor; MCT: monocarboxylate transporter; NHE1: Na + /H + exchanger 1HIGHLIGHTS Benzo[a]pyrene, a well-known environmental carcinogen, alters H + dynamics. NHE1 activation by B[a]P plays a key role in H + dynamics alterations. B[a]P-altered pH controls cell death/survival balance via mitochondria and lysosome. ABSTRACTDespite the improvement of diagnostic methods and anticancer therapeutics, the human population is still facing an increasing incidence of several types of cancers. According to the World Health Organization, this growing trend would be partly linked to our environment, with around 20% of cancers stemming from exposure to environmental contaminants, notably chemicals like polycyclic aromatic hydrocarbons (PAHs). PAHs are widespread pollutants in our environment resulting from incomplete combustion or pyrolysis of organic material, and thus produced by both natural and anthropic sources; notably benzo[a]pyrene (B[a]P), i.e. the prototypical molecule of this family, that can be detected in cigarette smoke, diesel exhaust particles, occupational-related fumes, and grilled food. This molecule is a well-recognized carcinogen belonging to group 1 carcinogens. Indeed, it can target the different steps of the carcinogenic process and all cancer hallmarks. Interestingly, H + dynamics have been described as key parameters for the occurrence of several, if not all, of these hallmarks. However, information regarding the role of such parameters during environmental carcinogenesis is still very scarce. The present review will thus mainly give an overview of the impact of B[a]P on H + dynamics in liver cells, and will show how such alterations might impact different aspects related to the finely-tuned balance between cell death and survival processes, thereby likely favoring environmental carcinogenesis. In total, the main objective of this review is to encourage further research in this poorly explored field of environmental molecular toxicology.

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Elimination of dysfunctional mitochondria through mitophagy suppresses benzo[a]pyrene-induced apoptosis

Cited by 62 publications

References 34 publications

The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor

The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor

Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)‐induced epithelial cytokine release through aryl hydrocarbon receptor in asthma

Disturbances in H+ dynamics during environmental carcinogenesis

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