Dysregulation of Gap Junction Function and Cytokine Production in Response to Non-Genotoxic Polycyclic Aromatic Hydrocarbons in an In Vitro Lung Cell Model

Romo, Deedee; Velmurugan, Kalpana; Upham, Brad L.; Dwyer‐Nield, Lori D.; Bauer, Alison K.

doi:10.3390/cancers11040572

Cited by 15 publications

(19 citation statements)

References 75 publications

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“…Studies have shown that connexins play a key role in mediating inflammation. For example, inflammation by polycyclic aromatic hydrocarbons in lung and liver epithelial cells results in the inhibition of gap junction intercellular communication through production of arachidonic acid, chemokines, TNF, and Cox-2 activation [17][18][19][20]. In activated peritoneal macrophages, inhibition Cx43 function through either pharmacologic administration or gene knockout improved survival, indicated by a reduction in cytokines during sepsis [21].…”

Section: Introductionmentioning

confidence: 99%

Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease

Cocozzelli

White

2019

IJMS

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Gap junctional channels are specialized components of the cellular membrane that allow the intercellular passage of small metabolites, ions, and second messengers to maintain homeostasis. They are comprised of members of the connexin gene family that encode a wide array of proteins that are expressed in nearly every tissue type. Cx43 is perceived to be the most broadly expressed connexin in humans, with several genetic skin diseases being linked to Cx43 mutations specifically. These mutations, in large, produce a gain of functional hemichannels that contribute to the phenotypes of Erythrokeratoderma Variabilis et Progressiva (EKVP), Palmoplantar Keratodemra Congenital Alopecia-1 (PPKCA1), and others that produce large conductance and increased permselectivity in otherwise quiescent structures. Gaining functional hemichannels can have adverse effects in the skin, inducing apoptosis via Ca2+ overload or increased ATP permeability. Here, we review the link between Cx43 and skin disease. We aim to provide insight into the mechanisms regulating the normal and pathophysiological gating of these essential proteins, as well as address current therapeutic strategies. We also demonstrate that transient transfection of neuro-2a (N2a) cells with mutant Cx43 cDNA resulted in increased hemichannel activity compared to wild-type Cx43 and untransfected cells, which is consistent with other studies in the current literature.

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Section: Introductionmentioning

confidence: 99%

Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease

Cocozzelli

White

2019

IJMS

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“…While it is well established that environmental DEPs have many toxic effects on cells and tissues of the cardio-pulmonary system [33,54], this study suggests that the stomach stem cells are also a target for DEPs. In an in vitro model of mGS cell exposure to DEPs, viability, migration, release of oxidative stress markers, and expression of some genes and proteins were systematically analyzed.…”

Section: Discussionmentioning

confidence: 58%

“…Little is known about the effects of DEPs on stem/progenitor cells. Exposure of stem/progenitor liver cells and lung cells to polycyclic aromatic hydrocarbons present in DEPs induce epigenetic toxicity characterized by a reduction in gap junctional intercellular communications and activation of MAPK activity and signaling pathways of both inflammation and carcinogenesis [ 31 , 32 , 33 , 34 ]. However, exposure of endothelial progenitor cells to DEPs impairs their number and migration and causes the formation of reactive oxygen species [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Diesel Exhaust Particles on Mouse Gastric Stem Cells

Al-Sadik

Sugathan

Saseedharan

et al. 2020

Life

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Stem cells have attracted many scientists because of their unique properties and therapeutic applications. However, very little is known on the environmental toxins that could affect their biological features. This study focuses on the consequences of the exposure of a cell line representative of the mouse gastric stem/progenitor (mGS) cells to diesel exhaust particles (DEPs). These immortal cells were cultured using routine protocols. The DEPs were added to the culture media at 1, 10, and 100 µg/mL for 1 to 72 h. The cells were assayed for their viability, migration, oxidative stress, and the expression of genes specific for cell proliferation, pluripotency, and death. DEPs induced a reduction in the metabolic activity of mGS cells, only at a high concentration of 100 µg/mL. However, no significant effects were detected on cell migration, oxidative stress markers (glutathione and thiobarbituric acid reactive substances), and cell death related proteins/genes. Interestingly, these findings were associated with down-regulation of Notch 2 and 3 and Bmi-1 proteins and activation of STAT3 involved in the regulation of the fate of stem cells. In conclusion, this study demonstrates that mGS cells have some resistance to oxidative stress and apoptosis when exposed to DEPs at the expense of their stemness.

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“…Probably, the example of lung cancers found in persons never having been exposed to tobacco smoke, either as a smoker or a downstream target. 41-43…”

Section: No One “Thing” Causes Human Cancersmentioning

confidence: 99%

What Can Chemical Carcinogenesis Shed Light on the LNT Hypothesis in Radiation Carcinogenesis?

Trosko

2019

Dose-Response

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To protect the public’s health from exposure to physical, chemical, and microbiological agents, it is important that any policy be based on rigorous scientifically based research. The concept of “linear no-threshold” (LNT) has been implemented to provide guideline exposures to these agents. The practical limitation to testing this hypothesis is to provide sufficient samples for experimental or epidemiological studies. While there is no universally accepted understanding of most human diseases, there seems to be better understanding of cancer that might help resolve the “LNT” model. The public’s concern, after being exposed to radiation, is the potential of producing cancer. The most rigorous hypothesis of human carcinogenesis is the “multistage, multimechanism” chemical carcinogenesis model. The radiation carcinogenesis LNT model, rarely, if ever, built it into their support. It will be argued that this multistage, multimechanism model of carcinogenesis, involving the “initiation” of a single cell by a mutagen event, followed by chronic exposure to threshold levels of epigenetic agents or conditions that stimulate the clonal expansion of the “initiated” cell, can convert these benign cells to become invasive and metastatic. This “promotion” process can be interrupted, thereby preventing these initiated cells from transitioning to the “progression” process of invasion and metastasis.

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Dysregulation of Gap Junction Function and Cytokine Production in Response to Non-Genotoxic Polycyclic Aromatic Hydrocarbons in an In Vitro Lung Cell Model

Cited by 15 publications

References 75 publications

Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease

Connexin 43 Mutations Lead to Increased Hemichannel Functionality in Skin Disease

Effects of Diesel Exhaust Particles on Mouse Gastric Stem Cells

What Can Chemical Carcinogenesis Shed Light on the LNT Hypothesis in Radiation Carcinogenesis?

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