Genetic Ablation of the Aryl Hydrocarbon Receptor Causes Cigarette Smoke-induced Mitochondrial Dysfunction and Apoptosis

Souza, Angela Rico de; Zago, Michela; Pollock, Stephen J.; Sime, Patricia J.; Phipps, Richard P.; Baglole, Carolyn J.

doi:10.1074/jbc.m111.258764

Cited by 78 publications

(82 citation statements)

References 71 publications

(88 reference statements)

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“…A decrease in ComplexIV activity has been reported in chronic human smokers [32]. Increased oxidative stress caused by CS, especially in the lung, also induces changes in mitochondrial functions, inducing apoptosis and alterations in bioenergetics [33]. Both nicotine and carbon monoxide have been implicated in altering mitochondrial dysfunction and metabolic injury.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

Raza¹,

John²,

Nemmar³

2013

Cell Physiol Biochem

42,541

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Background/Aims: The components of cigarette smoke (CS) have been implicated in the development of cancer as well as in cardiopulmonary diseases. We have previously reported increased oxidative stress in rat tissues induced by tobacco-specific toxins nicotine and 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Recently, we have also shown increased oxidative stress and associated inflammatory responses in various tissues after exposure to cigarette smoke. Methods: In this study, we have further investigated the effects of nose-only cigarette smoke exposure on mitochondrial functions and glutathione-dependent redox metabolism in tissues of BALB/C mice. Liver, kidney, heart and lung tissues were analyzed for oxidative stress, glutathione (GSH) and cytochrome P450 dependent enzyme activities and mitochondrial functions after exposure to smoke generated by 9 cigarettes/day for 4 days. Control mice were exposed to air only. Results: An increase in oxidative stress as observed by increased production of reactive oxygen species (ROS) and altered GSH metabolism was apparent in all the tissues, but lung and heart appeared to be the main targets. Increased expression and activity of CYP450 1A1 and 1A2 were also observed in the tissues after exposure to cigarette smoke. Mitochondrial respiratory dysfunction in the tissues, as observed by alterations in the activities of Complex I and IV enzymes, was also observed after exposure to cigarette smoke. SDS-PAGE and Western blot results also indicate that alterations in the expression of enzyme proteins were in accordance with the changes in their catalytic functions. Conclusion: These results suggest that even short term exposure of cigarette smoke have adverse effects on mitochondrial functions and redox homeostasis in tissues which may progress to further complications associated with chronic smoking.

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Section: Discussionmentioning

confidence: 99%

Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

Raza¹,

John²,

Nemmar³

2013

Cell Physiol Biochem

42,541

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“…In vivo mucus production enforces the physical protection of the lung epithelium. In another study, the AhR was demonstrated to protect fibroblasts from apoptosis caused by cigarette smoke (Rico de Souza et al, 2011). At the same time, AhR activity could be an integral part of a balanced immune response in the lung.…”

Section: Aryl Hydrocarbon Receptor In the Lungmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor in Barrier Organ Physiology, Immunology, and Toxicology

2015

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“…also cause oxidation of proteins, lipids, and DNA, leading to cellular damage and death (via apoptosis or necrosis) and also contributing to inflammation and chronic tissue damage (1,28,53,67,70). Thus, there is great interest in the use of antioxidants to prevent and treat smoking-related lung disease.…”

Section: L168 Inhibitors Of Acute Cigarette Smoke-induced Inflammationmentioning

confidence: 99%

“…CS contains high levels of free radicals and other reactive oxygen species (ROS) that contribute to proinflammatory activation of lung cells via NF-B and other redox-sensitive transcription factors (10,35,52,53). Additional ROS, including superoxide, H 2 O 2 , and hypochlorus acid, are released by inflammatory macrophages and neutrophils via the action of enzymes, including xanthine/xanthine oxidase, myeloperoxidase (MPO), and NADPH oxidase (30,69).…”

mentioning

confidence: 99%

Neu-164 and Neu-107, two novel antioxidant and anti-myeloperoxidase compounds, inhibit acute cigarette smoke-induced lung inflammation

Thatcher

Hsiao

Pinner

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Genetic Ablation of the Aryl Hydrocarbon Receptor Causes Cigarette Smoke-induced Mitochondrial Dysfunction and Apoptosis

Cited by 78 publications

References 71 publications

Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

Short-Term Effects of Nose-Only Cigarette Smoke Exposure on Glutathione Redox Homeostasis, Cytochrome P450 1A1/2 and Respiratory Enzyme Activities in Mice Tissues

The Aryl Hydrocarbon Receptor in Barrier Organ Physiology, Immunology, and Toxicology

Neu-164 and Neu-107, two novel antioxidant and anti-myeloperoxidase compounds, inhibit acute cigarette smoke-induced lung inflammation

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