L-cysteine attenuates peroxynitrite-elicited cytotoxicity to spiral ganglion neurons: possible relation to hearing loss.
Abstract
OBJECTIVES
The purpose of this work was to investigate whether L-cysteine was able to protect spiral ganglion neurons (SGNs) against
peroxynitrite (ONOO(-))-elicited toxicity.
METHODS
The rat SGNs were isolated and cultured in this work. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay. The morphological changes were examined under inverted phase contrast microscope. Cells underwent apoptosis
were determined by TdT-mediated dUTP nick end labeling (TUNEL) assay. Intracellular glutathione (GSH) content, superoxide
dismutase (SOD) activity and malonaldehyde (MDA) level were detected by biochemical methods. Laser scanning confocal microscope
was employed to analyze cytosolic Ca(2+) concentration.
RESULTS
Results showed that ONOO(-) reduced the cell viability of SGNs in a time- and dose-dependent manner. ONOO(-)-triggered cell
damage was further confirmed via apoptotic pathway rather than necrosis. Pretreatment with L-cysteine (5 mM) for 12 hours
could almost completely rescue SGNs from ONOO(-)-induced damage. The decrease in intracellular GSH content and SOD activity,
as well as the increase in MDA level induced by ONOO(-) were correspondingly antagonized by the administration of L-cysteine.
Furthermore, L-cysteine can significantly inhibit elevation of Ca(2+) concentration induced by ONOO(-).
DISCUSSION
Our findings indicate that L-cysteine protects SGNs from ONOO(-)-induced damage via enhancing the antioxidative activity and,
suppressing the lipid peroxidation as well as the release of cytosolic Ca(2+), thereby indicating that oxidation resistance
was useful to prevent audiological diseases initiated by oxidative stress.
Links
Authors
Lu S, Fan Z, Xu W, Han Y, Zhang G, Liu W, Bai X, Wang X, Xin H, Li J, Wang H
Institution
Institute of Eye and ENT, Provincial Hospital Affiliated to Shandong University, Jinan, China.
Source
Neurological research 33:9 2011 Nov pg 935-41MeSH
AnimalsAntioxidants
Cell Survival
Cells, Cultured
Cysteine
Hearing Loss
In Situ Nick-End Labeling
Microscopy, Confocal
Neurons
Oxidants
Peroxynitrous Acid
Rats
Spiral Ganglion
Pub Type(s)
Journal ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22080994
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