Human intestine epithelial cell acetyl- and butyrylcholinesterase

Sine, Jean‐Pierre; Ferrand, R; Cloarec, D; Lehur, Paul‐Antoine; Colas, Bernard

doi:10.1007/bf00233119

Cited by 25 publications

(18 citation statements)

References 15 publications

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“…In intestinal epithelium, ACh hydrolysis is catalyzed by a highly efficient acetylhydrolase, AChE (EC 3.1.1.7) (22). It is likely that we failed to detect ACh in H508 cell extracts because robust AChE activity rapidly hydrolyzed ACh.…”

Section: Discussionmentioning

confidence: 95%

Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation

Cheng

Samimi²,

Xie³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

131

116

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Most colon cancers overexpress M 3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor antagonists, acetylcholinesterase inhibitors, and choline transport inhibitors on cell proliferation. A nonselective muscarinic receptor antagonist (atropine), a selective M 3R antagonist (p-fluorohexahydro-sila-difenidol hydrochloride), and a choline transport inhibitor (hemicholinum-3) all inhibited unstimulated H508 colon cancer cell proliferation by ϳ40% (P Ͻ 0.005). In contrast, two acetylcholinesterase inhibitors (eserine-hemisulfate and bis-9-amino-1,2,3,4-tetrahydroacridine) increased proliferation by 2.5-and 2-fold, respectively (P Ͻ 0.005). By using quantitative real-time PCR, expression of choline acetyltransferase (ChAT), a critical enzyme for ACh synthesis, was identified in H508, WiDr, and Caco-2 colon cancer cells. By using high-performance liquid chromatography-electrochemical detection, released ACh was detected in H508 and Caco-2 cell culture media. Immunohistochemistry in surgical specimens revealed weak or no cytoplasmic staining for ChAT in normal colon enterocytes (n ϭ 25) whereas half of colon cancer specimens (n ϭ 24) exhibited moderate to strong staining (P Ͻ 0.005). We conclude that ACh is an autocrine growth factor in colon cancer. Mechanisms that regulate colon epithelial cell production and release of ACh warrant further investigation. autocrine signaling; choline acetyltransferase; muscarinic receptors FOR BOTH MEN AND WOMEN IN the United States colon cancer is a common, frequently lethal disease. Although endoscopic or surgical cancer resection is highly successful in treating early disease, advanced colon cancer responds poorly to surgery, chemotherapy, and radiation, thereby accounting for 30% mortality. A fundamental tenet of cancer biology is that elucidating mechanisms underlying neoplastic cell proliferation will identify therapeutic targets. Hence, identifying colon cancer growth factors and growth factor receptors is a prominent research goal. Nonetheless, although it was recognized more than 15 years ago that muscarinic receptor signaling stimulates colon cancer cell proliferation (9) and that most colon cancers overexpress M 3 muscarinic receptors (M 3 R) (29), muscarinic receptor ligands and receptors have been neglected as potential therapeutic targets.Postmuscarinic receptor signaling has long been recognized as integral to gastrointestinal physiology. Cholinergic nerve endings are present in colonic mucosa and muscarinic signaling, particularly via M 3 R, plays a prominent role in mediating intestinal epithelial fluid and electrolyte transport (10,26,28,30). Muscarinic receptor ...

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Section: Discussionmentioning

confidence: 95%

Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation

Cheng

Samimi²,

Xie³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

131

116

View full text Add to dashboard Cite

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“…Although it has long been known that the human bowels display AChE and BuChE activities [24], no information exists regarding the effects of cancer on them. The prevalence of BuChE over AChE activity in colorectal pieces, regardless of their anatomical localization (Table 1), contrasts with Sine's results.…”

Section: Discussionmentioning

confidence: 99%

Cholinesterases are down-expressed in human colorectal carcinoma

Montenegro

Ruíz-Espejo

Campoy

et al. 2006

Cell. Mol. Life Sci.

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The aberrations of cholinesterase (ChE) genes and the variation of ChE activity in cancerous tissues prompted us to investigate the expression of ChEs in colorectal carcinoma. The study of 55 paired specimens of healthy (HG) and cancerous gut (CG) showed that acetylcholinesterase (AChE) activity fell by 32% and butyrylcholinesterase (BuChE) activity by 58% in CG. Abundant AChE-H, fewer AChE-T, and even fewer AChE-R and BuChE mRNAs were observed in HG, and their content was greatly diminished in CG. The high level of the AChE-H mRNA explains the abundance of AChE-H subunits in HG, which as glycosylphosphatidylinositol (GPI)-anchored amphiphilic AChE dimers (G2(A)) and monomers (G1(A)) account for 69% of AChE activity. The identification of AChE-T and BuChE mRNAs justifies the occurrence in gut of A12, G4(H) and PRiMA-containing G4(A) AChE forms, besides G4(H), G4(A) and G1(H) BuChE. The down-regulation of ChEs might contribute to gut carcinogenesis by increasing acetylcholine availability and over-stimulating muscarinic receptors.

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“…In this context, it is interesting to note that acetylcholinesterase activity is present in some epithelia, including large bowel (Sine et al 1991), epidermis (Grando et al 1993), and amniotic epithelial cells (Sakuragawa et al 1997), and that ChAT is also capable of hydrolyzing acetylcholine (Molenaar 1990). Skin and amniotic epithelial cells have been shown both to contain ChAT and to metabolize acetylcholine (Grando et al 1993;Sakuragawa et al 1997).…”

Section: Figurementioning

confidence: 99%

Choline Acetyltransferase (ChAT) Immunoreactivity in Paraffin Sections of Normal and Diseased Intestines

Ratcliffe

Desa

Dixon

et al. 1998

J Histochem Cytochem.

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SUMMARYThere is increasing interest in localizing nerves in the intestine, especially specific populations of nerves. At present, the usual histochemical marker for cholinergic nerves in tissue sections is acetylcholinesterase activity. However, such techniques are applicable only to frozen sections and have uncertain specificity. Choline acetyltransferase (ChAT) is also present in cholinergic nerves, and we therefore aimed to establish a paraffin section immunocytochemical technique using an anti-ChAT antibody. Monoclonal anti-choline acetyltransferase (1.B3.9B3) and a biotin-streptavidin detection system were used to study the distribution of ChAT immunoreactivity (ChAT IR) in paraffin-embedded normal and diseased gastrointestinal tracts from both rats and humans. Optimal staining was seen after 6-24 hr of fixation in neutral buffered formalin and overnight incubation in 1 g/ml of 1.B3.9B3, with a similar distribution to that seen in frozen sections. In the rat diaphragm (used as a positive control), axons and motor endplates were ChAT IR. Proportions of ganglion cells and nerve fibers in the intramural plexi of both human and rat gastrointestinal tracts were also ChAT IR, as well as extrinsic nerve bundles in aganglionic segments of Hirschsprung's disease. Mucosal cholinergic nerves, however, were not visualized. In addition, non-neuronal cells such as endothelium, epithelium, and inflammatory cells were ChAT IR. We were able to localize ChAT to nerves in formalin-fixed, paraffin-embedded sections. The presence of ChAT IR in non-neuronal cells indicates that this method should be used in conjunction with other antibodies. Nevertheless, it proves to be a useful technique for studying cholinergic neuronal distinction in normal tissues and pathological disorders.

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Human intestine epithelial cell acetyl- and butyrylcholinesterase

Cited by 25 publications

References 15 publications

Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation

Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation

Cholinesterases are down-expressed in human colorectal carcinoma

Choline Acetyltransferase (ChAT) Immunoreactivity in Paraffin Sections of Normal and Diseased Intestines

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