Acetylcholinesterase in intestinal cell differentiation involves G2/M cell cycle arrest

Xiang, An-Li; Xie, Jing; Zhang, X. J.

doi:10.1007/s00018-008-8016-3

“…Previous studies have determined that apoptosis can also be induced in Caco-2 cells due to modification of phases of the cell cycle by redox modulation, specifically G1 to the S phase [41]. In a study by Xiang et al [42], butyrate increased the number of cells in the M phase and decreased cells in the S phase [42]. This inconsistency with the current study was possibly due to a lower dose of butyrate (1 m M ) and a shorter assay period [42].…”

Section: Discussionmentioning

confidence: 99%

“…In a study by Xiang et al [42], butyrate increased the number of cells in the M phase and decreased cells in the S phase [42]. This inconsistency with the current study was possibly due to a lower dose of butyrate (1 m M ) and a shorter assay period [42]. However, Matthews et al [1] demonstrated that butyrate (5 m M ) treatment of Caco-2 cells reduced cells in G0/G1 and arrested cells in the S and G2/M phases [1].…”

Section: Discussionmentioning

confidence: 99%

Induction of Apoptosis by the Medium-Chain Length Fatty Acid Lauric Acid in Colon Cancer Cells due to Induction of Oxidative Stress

Fauser

¹

,

Matthews²,

Cummins³

et al. 2013

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Background: Fatty acids are classified as short-chain (SCFA), medium-chain (MCFA) or long-chain and hold promise as adjunctive chemotherapeutic agents for the treatment of colorectal cancer. The antineoplastic potential of MCFA remains underexplored; accordingly, we compared the MCFA lauric acid (C12:0) to the SCFA butyrate (C4:0) in terms of their capacity to induce apoptosis, modify glutathione (GSH) levels, generate reactive oxygen species (ROS), and modify phases of the cell cycle in Caco-2 and IEC-6 intestinal cell lines. Methods: Caco-2 and IEC-6 cells were treated with lauric acid, butyrate, or vehicle controls. Apoptosis, ROS, and cell cycle analysis were determined by flow cytometry. GSH availability was assessed by enzymology. Results: Lauric acid induced apoptosis in Caco-2 (p < 0.05) and IEC-6 cells (p < 0.05) compared to butyrate. In Caco-2 cells, lauric acid reduced GSH availability and generated ROS compared to butyrate (p < 0.05). Lauric acid reduced Caco-2 and IEC-6 cells in G0/G1and arrested cells in the S and G2/M phases. Lauric acid induced apoptosis in IEC-6 cells compared to butyrate (p < 0.05). Butyrate protected IEC-6 cells from ROS-induced damage, whereas lauric acid induced high levels of ROS compared to butyrate. Conclusion: Compared to butyrate, lauric acid displayed preferential antineoplastic properties, including induction of apoptosis in a CRC cell line.

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“…This esterase activity is the target of widely used pesticides and pharmaceuticals (Mileson et al, 1998;Pope et al, 2005), yet the broad expression of AChE outside of the nervous system (Anderson et al, 2008;Bertrand et al, 2001;Bicker et al, 2004;Drews, 1975) and similarity to adhesion molecules (Botti et al, 1998;Darboux et al, 1996) suggest that it has additional functions. Indeed, in neuronal and non-neuronal cell lines, AChE promotes cell-substrate adhesion (Inkson et al, 2004;Johnson and Moore, 1999;Sharma et al, 2001;Syed et al, 2008), polarized cell migration (Anderson et al, 2008), cytoskeletal organization (Dupree and Bigbee, 1994;Keller et al, 2001) and cell differentiation (Grisaru et al, 1999;Xiang et al, 2008), independently of its esterase activity (Layer et al, 1993). However, the in vivo relevance of this putative multi-functionality is poorly substantiated, especially in non-neuronal contexts (Vogel-Hopker et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis

Pickett

¹

,

Dush

²

,

Nascone-Yoder

³

2017

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Acetylcholinesterase (AChE) is crucial for degrading acetylcholine at cholinergic synapses. In vitro studies suggest that, in addition to its role in nervous system signaling, AChE can also modulate nonneuronal cell properties, although it remains controversial whether AChE functions in this capacity in vivo. Here, we show that AChE plays an essential non-classical role in vertebrate gut morphogenesis. Exposure of Xenopus embryos to AChE-inhibiting chemicals results in severe defects in intestinal development. Tissuetargeted loss-of-function assays (via microinjection of antisense morpholino or CRISPR-Cas9) confirm that AChE is specifically required in the gut endoderm tissue, a non-neuronal cell population, where it mediates adhesion to fibronectin and regulates cell rearrangement events that drive gut lengthening and digestive epithelial morphogenesis. Notably, the classical esterase activity of AChE is dispensable for this activity. As AChE is deeply conserved, widely expressed outside of the nervous system, and the target of many environmental chemicals, these results have wide-reaching implications for development and toxicology.

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“…This esterase activity is the target of widely used pesticides and pharmaceuticals (Mileson et al, 1998;Pope et al, 2005), yet the broad expression of AChE outside of the nervous system (Anderson et al, 2008;Bertrand et al, 2001;Bicker et al, 2004;Drews, 1975) and similarity to adhesion molecules (Botti et al, 1998;Darboux et al, 1996) suggest that it has additional functions. Indeed, in neuronal and non-neuronal cell lines, AChE promotes cell-substrate adhesion (Inkson et al, 2004;Johnson and Moore, 1999;Sharma et al, 2001;Syed et al, 2008), polarized cell migration (Anderson et al, 2008), cytoskeletal organization (Dupree and Bigbee, 1994;Keller et al, 2001) and cell differentiation (Grisaru et al, 1999;Xiang et al, 2008), independently of its esterase activity (Layer et al, 1993). However, the in vivo relevance of this putative multi-functionality is poorly substantiated, especially in non-neuronal contexts (Vogel-Hopker et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis

Pickett¹,

Dush²,

Nascone-Yoder³

2017

Journal of Cell Science

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) is crucial for degrading acetylcholine at cholinergic synapses. In vitro studies suggest that, in addition to its role in nervous system signaling, AChE can also modulate nonneuronal cell properties, although it remains controversial whether AChE functions in this capacity in vivo. Here, we show that AChE plays an essential non-classical role in vertebrate gut morphogenesis. Exposure of Xenopus embryos to AChE-inhibiting chemicals results in severe defects in intestinal development. Tissuetargeted loss-of-function assays (via microinjection of antisense morpholino or CRISPR-Cas9) confirm that AChE is specifically required in the gut endoderm tissue, a non-neuronal cell population, where it mediates adhesion to fibronectin and regulates cell rearrangement events that drive gut lengthening and digestive epithelial morphogenesis. Notably, the classical esterase activity of AChE is dispensable for this activity. As AChE is deeply conserved, widely expressed outside of the nervous system, and the target of many environmental chemicals, these results have wide-reaching implications for development and toxicology.

show abstract

Acetylcholinesterase in intestinal cell differentiation involves G2/M cell cycle arrest

Cited by 22 publications

References 26 publications

Induction of Apoptosis by the Medium-Chain Length Fatty Acid Lauric Acid in Colon Cancer Cells due to Induction of Oxidative Stress

Induction of Apoptosis by the Medium-Chain Length Fatty Acid Lauric Acid in Colon Cancer Cells due to Induction of Oxidative Stress

Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis

Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis

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