title: Acetylcholine esterase is a regulator of GFAP expression and a target of dichlorvos in astrocytic differentiation of rat glioma C6 cells.
abstract: The main target of neurotoxins is neurons because they comprise the main part of neural function, but glial cells may be indirect targets because they support the function of neurons. Among the glial cells, astrocytes in particular act as "nurse cells", regulating neuronal survival and functions. In the present study, to reveal whether a known neurotoxic substance, organophosphate dichlorvos (DDVP), affects the differentiation of astrocytes, we used an astrocyte differentiation model in rat glioma C6 cells. Morphological change and induction of GFAP expression in the differentiating C6 cells were suppressed by DDVP treatment. The known potential targets of DDVP are acetylcholine esterase (AChE), fatty acid amide hydrolase and methyl guanine methyl transferase. Among the specific inhibitors against these enzymes, the AChE inhibitor paraoxon successfully suppressed the cellular morphological changes and the induction of GFAP expression in differentiating C6 cells. These results indicate that DDVP inhibits differentiation in the C6 astrocyte-differentiation model, in which at least AChE inhibition is involved and that AChE is a potent regulator of the differentiation. Furthermore, considering that the main substrate of AChE is ACh, thus, ACh may act as regulators of astrocyte differentiation.
authors.affiliation: Department of Anatomy II, School of Veterinary Medicine, Azabu University, Sagamihara 229-8501, Japan.
authors.forename: Aisa
authors.initials: A
authors.lastname: Ozawa
authors.forename: Erina
authors.initials: E
authors.lastname: Kadowaki
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Haga
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sekiguchi
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hemmi
authors.forename: Takuya
authors.initials: T
authors.lastname: Kaneko
authors.forename: Takehiro
authors.initials: T
authors.lastname: Maki
authors.forename: Kou
authors.initials: K
authors.lastname: Sakabe
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Masako
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Arishima
authors.forename: Motoharu
authors.initials: M
authors.lastname: Sakaue
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004006:Dichlorvos / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects* / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D005904:Glial Fibrillary Acidic Protein; D004006:Dichlorvos; D000242:Cyclic AMP; D000110:Acetylcholinesterase
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; ACh; ACh esterase; AChE; Acetylcholine; Acetylcholine esterase; Astrocyte; DDVP; FAAH; GFAP; MGMT; MTT; N6,2′-O-dibutyryladenosine-3′5′-cyclic monophosphate sodium salt; NTE; OPIDN; acetylcholine; cAMP; cyclic adenosine monophosphate; dbcAMP; dichlorvos; fatty acid amide hydrolase; glial fibrillary acidic protein; methyl guanine methyl transferase; neuropathy target esterase; organophosphate-induced delayed neuropathy