title: Modulation of the canonical Wnt pathway by Benzalkonium Chloride in corneal epithelium.
abstract: Benzalkonium Chloride (BAC) is commonly used in eyedrops. Although the cytotoxicity of BAC has been reported, the mechanism underlying its toxic effect has not been elucidated. The present study investigated the role of the Wnt signaling pathway in the cytotoxicity of BAC in corneal epithelial cells and in the rat cornea. We demonstrated that phosphorylation of β-catenin, a downstream effector of the canonical Wnt pathway, was down-regulated by a short exposure to BAC in both cultured human corneal epithelial cells (HCE) and a cultured mouse corneal epithelial progenitor cell line (TKE2), suggesting an activation of the Wnt pathway. The activation of Wnt pathway is correlated with the decrease of cell viability induced by BAC. On the other hand, a specific Wnt pathway inhibitor, secreted frizzled-related protein-1 (sFRP1), reversed BAC-induced down-regulating effects on the level of phosphorylation of β-catenin and ameliorated cell viability in cells treated with BAC. In the rat cornea, the levels of total β-catenin were significantly up-regulated 8 h after the topical administration of BAC. Taken together, these results provided novel evidence suggesting that the cytotoxicity of BAC may be mediated through modulation of the Wnt pathway.
authors.affiliation: Eye Institute of Xiamen University, Key Laboratory of Fujian Province in Ophthalmology and Visual Science Research, Xiamen 361005, PR China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Lin
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Shao
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Liu
authors.forename: Jian-xing
authors.initials: JX
authors.lastname: Ma
authors.forename: Zuguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001548:Benzalkonium Compounds / Q000633:toxicity*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011310:Preservatives, Pharmaceutical / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D001548:Benzalkonium Compounds; C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D011310:Preservatives, Pharmaceutical; D051153:Wnt Proteins; D051176:beta Catenin