Pyridoxine Preferentially Induces Auditory Neuropathy Through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress-Mediated Apoptosis. (June 2019)

• Record Type: Journal Article
• Authors: Park, Channy; Lim, Hyewon; Moon, Sung K.; Park, Raekil
• Other Names: Moon Sung K. guest-editor.; Kawauchi Hideyuki guest-editor.; Oh Seung-Ha guest-editor.
• Is Part Of: Annals of otology, rhinology & laryngology. Volume 128(2019)Supplement 6
• Page Start: 117S
• Page End: 124S
• Publication Date: 2019-06
• Subjects: pyridoxine -- auditory neuropathy -- VOT-33 -- mitochondrial dysfunction -- ER stress; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0003489419836116
• Languages: English
• ISSNs: 0003-4894

Abstract

Objectives: Auditory neuropathy due to toxicity mechanism of pyridoxine has not yet been fully documented. Therefore, the present study explored a direct mechanism underlying the effects of pyridoxine on auditory neuropathy in organ of Corti (OC) explants ex vivo and cochlear neuroblast cell line, VOT-33 in vitro. Methods: Primary OC explants containing spiral ganglion neurons and cultured VOT-33 cells were treated with pyridoxine. Results: In nerve fiber of primary OC explants, pyridoxine decreased staining for NF200, a neuro-cytoskeletal protein. We also found that pyridoxine-induced VOT-33 apoptosis, as indicated by accumulation of the sub-G0/G1 fraction, caspase-3 activation, and PARP cleavage. In addition, pyridoxine induced reactive oxygen species (ROS) generation and alteration of mitochondrial membrane potential transition (MPT), including Bcl-2 family protein expression and consequently Ca 2+ accumulation and changes of endoplasmic reticulum (ER) stress-related protein expression such as phospho-PERK, caspase-12, Grp78, and CHOP. Conclusion: Pyridoxine preferentially induced severe cell death on nerve fiber in primary OC explants and markedly increased apoptotic cell death via mitochondria-mediated ER stress in VOT-33 cells.