Modulation of choline acetyltransferase synthesis by okadaic acid, a phosphatase inhibitor, and KN-62, a CaM kinase inhibitor, in NS-20Y neuroblastoma

Pahud, Gabrielle; Bontron, Séverine; Eder-Colli, Lorenza

doi:10.1016/s0197-0186(00)00064-4

Cited by 8 publications

(6 citation statements)

References 20 publications

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“…Short-term exposure to phosphatase inhibitors (calyculin A or okadaic acid) reduced ACh synthesis and ChAT activity in brain slices [34]. More recently, it has been shown that in NS-20y cells okadaic acid induces an increase of ChAT activity after a 24 h treatment, possibly due to an accumulation of ChAT mRNA [35]. Phosphorylation by casein kinase II and protein kinase C (PKC) increased enzyme activity, whereas alpha-calcium/calmodulindependent kinase phosphorylated ChAT, but did not change it [36].…”

Section: The Biosynthetic Pathwaymentioning

confidence: 99%

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Amenta¹,

Tayebati

2008

CMC

119

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Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.

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Section: The Biosynthetic Pathwaymentioning

confidence: 99%

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Amenta¹,

Tayebati

2008

CMC

119

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“…A smaller ChAT protein (molecular weight of 27 kDa) has also been characterized. This protein lacks catalytic activity but is believed have a regulatory role on the activity of fulllength ChAT (Grosman, Lorenzi, Trinidad, & Strauss, 1995 Eder-Colli, 2001;Schmidt, 1993). SNPs in the ChAT gene have been correlated with nicotine dependence and prospective smoking cessation (R. Ray, et al, 2010).…”

Section: Choline Acetyltransferase (Chat)mentioning

confidence: 99%

Acetylcholine signaling system in progression of lung cancers

Friedman

Richbart

Merritt

et al. 2019

Pharmacology & Therapeutics

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The neurotransmitter acetylcholine (ACh) acts as an autocrine growth factor for human lung cancer. Several lines of evidence show that lung cancer cells express all of the proteins required for the uptake of choline (choline transporter 1, choline transporter-like proteins) synthesis of ACh (choline acetyltransferase, carnitine acetyltransferase), transport of ACh (vesicular acetylcholine transport, OCTs, OCTNs) and degradation of ACh (acetylcholinesterase, butyrylcholinesterase). The released ACh binds back to nicotinic (nAChRs) and muscarinic receptors on lung cancer cells to accelerate their proliferation, migration and invasion. Out of all components of the cholinergic pathway, the nAChR-signaling has been studied the most intensely. The reason for this trend is due to genome-wide data studies showing that nicotinic receptor subtypes are involved in lung cancer risk, the relationship between cigarette smoke and lung cancer risk as well as the rising popularity of electronic cigarettes considered by many as a "safe" alternative to smoking. There are a small number of review articles which review the contribution of the other cholinergic proteins in the pathophysiology of lung cancer. The primary objective of this review article is to discuss the function of the acetylcholine-signaling proteins in the progression of lung cancer. The investigation of the role of cholinergic network in lung cancer will pave the way to novel molecular targets and drugs in this lethal malignancy.

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“…Changes in ChAT mRNA levels have been used to evaluate enzyme response to stimuli (28,30). Hypothyroidism induces Fos expression in about 50% of ChAT neurons in the DMV, suggesting the possibility of elevated ChAT gene expression.…”

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confidence: 99%

Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain medullary dorsal vagal complex in rats

Yuan¹,

Yang²

2005

American Journal of Physiology-Endocrinology and Metabolism

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Hypo-or hyperthyroidism is associated with autonomic disorders. We studied Fos expression in the medullary dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarii (NTS), and area postrema (AP) in four groups of rats with different thyroid states induced by a combination of drinking water and daily intraperitoneal injection for 1-4 wk: 1) tap water and vehicle; 2) 0.1% propylthiouracil (PTU) and vehicle; 3) PTU and thyroxine (T 4; 2 g/100 g); and 4) tap water and T 4 (10 g/100 g). The numbers of Fos immunoreactive (IR) positive neurons in the DMV, NTS, and AP were low in euthyroid rats but significantly higher in the 4-wk duration in hypothyroid rats, which were prevented by simultaneous T4 replacement. Hyperthyroidism had no effect on Fos expression in these areas. There were significant negative correlations between T4 levels and the numbers of Fos-IRpositive neurons in the DMV (r ϭ Ϫ0.6388, P Ͻ 0.008), NTS (r ϭ Ϫ0.6741, P Ͻ 0.003), and AP (r ϭ Ϫ0.5622, P Ͻ 0.004). Double staining showed that Fos immunoreactivity in the DMV of hypothyroid rats was mostly localized in choline acetyltransferase-containing neurons. Thyroid hormone receptors ␣1 and ␤2 were localized in the observed nuclei. These results indicate that thyroid hormone influences the DMV/NTS/AP neuronal activity, which may contribute to the vagal-related visceral disorders observed in hypothyroidism. thyroid hormone; dorsal motor nucleus of the vagus; nucleus tractus solitarii; vagus nerve; area postrema HYPOTHYROIDISM IS A PREVALENT DISEASE worldwide and has a high incidence in elderly patients with nonthyroidal disease (3, 39). Extensive cardiovascular, gastrointestinal (GI), and metabolic disorders, such as sinus bradycardia, altered GI secretion and motility, and hyperlipidemia are the main clinical symptoms of hypothyroidism. These symptoms indicate autonomic dysfunction with a relative vagal dominance (43, 44) and correlate to increased mortality from cardiovascular and cerebrovascular diseases in those with a history of overt or subclinical thyroid disorders (29, 39). How thyroid hormone regulates vagal activities, particularly the central mechanism, is still poorly understood.On the basis of solidly established physiological role of medullary thyrotropin-releasing hormone (TRH)-containing vagal regulatory pathways in the central regulation of GI functions (47), we recently revealed that feedback regulation of TRH gene expression by thyroid hormone in the medullary raphe pallidus (Rpa), raphe obscurus (Rob), and parapyramidal region (PPR) may contribute to hypothyroidism-induced autonomic disorders (49 -52). TRH-containing projections arising from these nuclei innervate the dorsal vagal complex (DVC) (20) and the sympathetic motor neurons in the intermediolateral cell column of the spinal cord (40). Our previous studies showed that hypothyroidism increases TRH mRNA levels in the Rpa, Rob, and PPR and induces Fos expression, a widely accepted parameter indicating brain neuronal activation, in the TRH-synthesizing neurons in these nucl...

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Modulation of choline acetyltransferase synthesis by okadaic acid, a phosphatase inhibitor, and KN-62, a CaM kinase inhibitor, in NS-20Y neuroblastoma

Cited by 8 publications

References 20 publications

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Acetylcholine signaling system in progression of lung cancers

Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain medullary dorsal vagal complex in rats

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