Neurite Differentiation Is Modulated in Neuroblastoma Cells Engineered for Altered Acetylcholinesterase Expression

Koenigsberger, Carol; Chiappa, Sharon A.; Brimijoin, Stephen

doi:10.1046/j.1471-4159.1997.69041389.x

Cited by 129 publications

(101 citation statements)

References 21 publications

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“…AChE is predominantly expressed in cholinergic tissues (muscle and neurons); however, it is also expressed in some noncholinergic neurons and nonexcitable cells, such as hematopoietic cells (Hammond et al, 1994;Bernard et al, 1995;Brimijoin and Hammond, 1996;Lev-Lehman et al, 1997;Chan et al, 1998). As a result, several noncholinergic roles have been described for AChE including in neurite elongation, cell adhesion, and synaptogenesis (Brimijoin and Hammond, 1996;Koenigsberger et al, 1997;Grifman et al, 1998;Sternfeld et al, 1998;Lev-Lehman et al, 2000;Sharma et al, 2001) (for review, see Soreq and Seidman, 2001). In addition to having these nonclassical roles, AChE and its different molecular forms have been implicated in the development of neuronal tumors, in Alzheimer's disease, and in post-traumatic stress disorder (Karpel et al, 1994;Kaufer et al, 1998;Perry et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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After axotomy, expression of acetylcholinesterase (AChE) is greatly reduced in the superior cervical ganglion (SCG); however, the molecular events involved in this response remain unknown. Here, we first examined AChE mRNA levels in the brain of transgenic mice that overexpress human HuD. Both in situ hybridization and reverse transcription-PCR demonstrated that AChE transcript levels were increased by more than twofold in the hippocampus of HuD transgenic mice. Additionally, direct interaction between the HuD transgene product and AChE mRNA was observed. Next, we examined the role of HuD in regulating AChE expression in intact and axotomized rat SCG neurons. After axotomy of the adult rat SCG neurons, AChE transcript levels decreased by 50 and 85% by the first and fourth day, respectively. In vitro mRNA decay assays indicated that the decrease in AChE mRNA levels resulted from changes in the stability of presynthesized transcripts. A combination of approaches performed using the region that directly encompasses an adenylate and uridylate (AU)-rich element within the AChE 3Ј-untranslated region demonstrated a decrease in RNA-protein complexes in response to axotomy of the SCG and, specifically, a decrease in HuD binding. After axotomy, HuD transcript and protein levels also decreased. Using a herpes simplex virus construct containing the human HuD sequence to infect SCG neurons in vivo, we found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy. Together, the results of this study demonstrate that AChE expression in neurons of the rat SCG is regulated via post-transcriptional mechanisms that involve the AU-rich element and HuD.

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Section: Introductionmentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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“…AChE is involved in cell adhesion, proliferation, and neurite outgrowth in diverse types of neurons, including non-cholinergic neurons [Karpel et al, 1996;Koenigsberger et al, 1997;Day and Greenfield, 2002;Whyte and Greenfield, 2003;Johnson and Moore, 2004]. In the hematopoietic system, AChE inhibits proliferation of multipotent stem cells and regulates apoptosis .…”

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confidence: 99%

Differential localization of acetylcholinesterase in neuronal and non‐neuronal cells

Thullbery

Cox

Schule

et al. 2005

J of Cellular Biochemistry

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Acetylcholinesterase (AChE) expression is regulated in cell types at the transcriptional and translational levels. In this study, we characterized and compared AChE catalytic activity, mRNA, protein expression, and protein localization in a variety of neuronal (SH-SY5Y neuroblastoma and primary cerebellar granule neurons (CGN)) and non-neuronal (LLC-MK2, HeLa, THP-1, and primary astrocytes) cell types. All cell lines expressed AChE catalytic activity; however the levels of AChE-specific activity were higher in neuronal cells than in the non-neuronal cell types. CGN expressed significantly more AChE activity than SH-SY5Y cells. All cell lines analyzed expressed AChE protein at equivalent levels, as well as mRNA splice variants. Localization of AChE was characterized by immunofluorescence and confocal microscopy. SH-SY5Y, CGN, and nerve-growth factor-differentiated PC-12 cells exhibited a pattern of AChE localization characterized as diffuse in the cytoplasm and punctate staining along neurites and on the plasma membrane. The localization in HeLa, LLC-MK2, fibroblasts, and undifferentiated PC-12 cells was significantly different than in neuronal cells-AChE was intensely localized in the perinuclear region, without staining near or on the plasma membrane. Based on the evidence presented here, we hypothesize that the presence of AChE protein doesn't correlate with catalytic activity, and the diffuse cytoplasmic and plasma membrane localization of AChE is a property of neuronal cell types. Keywords acetylcholinesterase; confocal microscopy; cerebellar granule neuron; neuroblastoma; SH-SY5Y; HeLa; PC-12 Acetylcholinesterase (AChE) belongs to the serine hydrolase family that contains the α/β hydrolase fold as a common structural element [Ollis et al., 1992]. The catalytic active site of AChE is made up of a precise arrangement of active site functional groups that catalyze the hydrolytic breakdown of esters that bear quaternary ammonium groups. The biological importance of AChE-catalyzed hydrolysis is manifested in the rapid termination of the neuronal impulse that occurs when acetylcholine (ACh) is released into the synaptic cleft. AChE rapidly hydrolyzes ACh into acetic acid and choline at extremely fast turnover rates [Taylor and Radic, 1994].

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“…These agents, although all sharing anticholinesterase activity, actually have very different structures and belong to separate classes of cholinesterase inhibitors. Cholinesterase is now known to play a nonenzymatic, structural role in neural assembly [3,31], and the disparities seen here in the sea urchin model could thus reflect different conformational changes in cholinesterase engendered by its interaction with structurallydiverse inhibitors. Alternatively, each of these agents also possesses properties other than cholinesterase inhibition that can contribute to adverse outcomes.…”

Section: Discussionmentioning

confidence: 89%

Amyloid precursor protein 96–110 and β-amyloid 1–42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids

Buznikov

Nikitina

Seidler

et al. 2008

Neurotoxicology and Teratology

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Amyloid precursor protein (APP) is overexpressed in the developing brain and portions of its extracellular domain, especially amino acid residues 96-110, play an important role in neurite Correspondence: Dr. T.A. Slotkin, Dept. of Pharmacology & Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710-3813, Tel (919) 681 8015, Fax (919) 684 8197, e-mail: t.slotkin@duke.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. outgrowth and neural cell differentiation. In the current study, we evaluated the developmental abnormalities caused by administration of exogenous APP 96-110 in sea urchin embryos and larvae, which, like the developing mammalian brain, utilize acetylcholine and other neurotransmitters as morphogens; effects were compared to those of β-amyloid 1-42 (Aβ42), the neurotoxic APP fragment contained within neurodegenerative plaques in Alzheimer's Disease. Although both peptides elicited dysmorphogenesis, Aβ42 was far more potent; in addition, whereas Aβ42 produced abnormalities at developmental stages ranging from early cleavage divisions to the late pluteus, APP 96-110 effects were restricted to the intermediate, mid-blastula stage. For both agents, anomalies were prevented or reduced by addition of lipid-permeable analogs of acetylcholine, serotonin or cannabinoids; physostigmine, a carbamate-derived cholinesterase inhibitor, was also effective. In contrast, agents that act on NMDA receptors (memantine) or α-adrenergic receptors (nicergoline), and that are therapeutic in Alzheimer's Disease, were themselves embryotoxic, as was tacrine, a cholinesterase inhibitor from a different chemical class than physostigmine. Protection was also provided by agents acting downstream from receptor-mediated events: increasing cyclic AMP with caffeine or isobutylmethylxanthine, or administering the antioxidant, α-tocopherol, were all partially effective. Our findings reinforce a role for APP in development and point to specific interactions with neurotransmitter systems that act as morphogens in developing sea urchins as well as in the mammalian brain. NIH Public Access

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Neurite Differentiation Is Modulated in Neuroblastoma Cells Engineered for Altered Acetylcholinesterase Expression

Cited by 129 publications

References 21 publications

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Differential localization of acetylcholinesterase in neuronal and non‐neuronal cells

Amyloid precursor protein 96–110 and β-amyloid 1–42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids

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