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

Park C1, Lim H2, Moon SK3, Park R1.

Author information

1

1 Laboratory of Peroxisomes & Lipid Metabolism, Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.

2

2 Department of Obstetrics and Gynecology, Iksan Hospital, Jeonbuk, Korea.

3

3 Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

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 Ca2+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.

KEYWORDS:

ER stress; VOT-33; auditory neuropathy; mitochondrial dysfunction; pyridoxine

PMID:

 

31092035

 

DOI:

 

10.1177/0003489419836116

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