Recent progress in understanding the non-neuronal cholinergic system in humans

Grando, Sergei A.; Kawashima, Koichiro; Kirkpatrick, Charles James; Wessler, Ignaz

doi:10.1016/j.lfs.2007.03.015

Cited by 48 publications

(35 citation statements)

References 55 publications

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“…The transformed epithelial cells have a functional non-neuronal cholinergic system for signal transduction with acetylcholine as a single extracellular messenger, or a cytotransmitter (reviewed in [22]). The existence of a cholinergic autocrine loop in epithelial cells explains certain aspects of the carcinogenic effects of tobacco products, and provides a basis for identification of new targets for potential therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of SLURP-1 and -2 alleviates the tumorigenic action of tobacco-derived nitrosamine on immortalized oral epithelial cells

Arredondo

Chernyavsky

Grando

2007

Biochemical Pharmacology

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Recent research has demonstrated that mucocutaneous epithelial cells express functional nicotinic acetylcholine receptors (nAChRs) and that tobacco-derived carcinogenic nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and SLURP (secreted mammalian Ly-6/ urokinase plasminogen activator receptor-related protein)-1 and -2 can act as non-canonical ligands of these receptors. It was found that recombinant SLURP-1 and -2 can lessen tumorigenic activity of nitrosamines. The immortalized esophageal keratinocytes (Het-1A cells) exhibit low SLURP-1 and -2 mRNA levels that decrease further after treatment with NNK. Based on these observations, we hypothesized that overexpression of full length SLURP proteins may protect Het-1A cells from malignant transformation by NNK. The Het-1A cells transfected with either SLURP-1 or -2 vector produced the highest amounts of respective proteins between 24 and 48 h, at which point they were exposed to 1 μM NNK for 24 h and their tumorigenic activities were subsequently evaluated by plating in soft agar and injecting subcutaneously to Nu/Nu mice. Transfection with either SLURP-1 or -2 cDNA in both cases significantly (p<0.05) diminished the number of colonies produced by NNK exposed cells. SLURP-1 was more efficient than SLURP-2 in abolishing the tumorigenic effect in nude mice. Thus, the anti-tumorigenic activities of SLURP-1 and -2 were demonstrated both in vitro and in vivo. The obtained results suggest that SLURP-like proteins may become useful for developing novel anti-cancer therapies.

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Section: Discussionmentioning

confidence: 99%

Overexpression of SLURP-1 and -2 alleviates the tumorigenic action of tobacco-derived nitrosamine on immortalized oral epithelial cells

Arredondo

Chernyavsky

Grando

2007

Biochemical Pharmacology

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“…macrophages, T-lymphocytes and epithelial cells [169]. This suggests that anticholinergics have the potential for antiinflammatory effects in COPD, particularly since tiotropium bromide reduces exacerbations.…”

Section: -4xmentioning

confidence: 99%

Systemic manifestations and comorbidities of COPD

Barnes¹,

Celli²

2009

European Respiratory Journal

1,470

1,113

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Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the ''spill-over'' of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

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“…All the neuronal components, ACh, ChAT and VAChT and AChE above mentioned, are also present in the NNCS [9].…”

Section: Non-neuronal Cholinergic System (Nncs)mentioning

confidence: 95%

“…Non-neuronal acetylcholine appears to be involved in the regulation of elementary cell functions such as cell mitosis, cell-cell interaction, cell automaticity, locomotion, ciliary activity, barrier function, resorption and secretion [29][30][31][32][33]. In the airways, for instance, the great majority of cells express the components of NNCS and it is documented that a substantial increase on ACh levels triggers the release of proinflammatory effectors [34].…”

Section: Non-neuronal Cholinergic System (Nncs)mentioning

confidence: 99%