title: Green Tea Polyphenols Protects Cochlear Hair Cells from Ototoxicity by Inhibiting Notch Signalling.
abstract: Notch signalling pathway plays an essential role in the development of cochlea, which inhibits the proliferation of hair cells. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea, which presents strong antioxidant activation and has been applied for anti-cancer and anti-inflammatory. In this study, we treated the cochlear explant cultures with EGCG and found that EGCG can protect cochlear hair cells from ototoxic drug gentamicin. We demonstrated that EGCG could down-regulate the expression of Notch signalling pathway target genes, such as Hes1, Hes5, Hey1 and Hey5. However, the Notch pathway ligands such as Delta1, Jag1 and Jag2 were not affected by EGCG. To further illustrate the mechanism of recover cochlear hair cells, we demonstrated that EGCG inhibited the activity of γ-secrectase to suppress Notch signalling pathway and promoted the proliferation and regeneration of hair cells in the damaged cochlea. Our results suggest for the first time the role of EGCG as an inhibitor of the Notch signalling pathway, and support its potential value in hearing-impaired recovery in clinical therapy.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Qianfo Shan Hospital Affiliated to Shandong University, Jinan, 250014, People's Republic of China.
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Gu
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.forename: Shi-Zheng
authors.initials: SZ
authors.lastname: Su
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Liu
authors.forename: Zhong-Gang
authors.initials: ZG
authors.lastname: Shi
authors.forename: Qi-Rong
authors.initials: QR
authors.lastname: Wang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003051:Cochlea / Q000293:injuries; D015536:Down-Regulation / Q000187:drug effects; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D040542:Mechanotransduction, Cellular; D051379:Mice; D008822:Mice, Transgenic; D059808:Polyphenols / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D051880:Receptors, Notch / Q000037:antagonists & inhibitors*; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*
chemical_list: D005839:Gentamicins; D059808:Polyphenols; D011500:Protein Synthesis Inhibitors; D051880:Receptors, Notch; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D053829:Amyloid Precursor Protein Secretases