title: L-cysteine attenuates peroxynitrite-elicited cytotoxicity to spiral ganglion neurons: possible relation to hearing loss.
abstract: OBJECTIVE
  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(-).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Eye and ENT, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Lu
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Fan
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Yuechen
authors.initials: Y
authors.lastname: Han
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Xin
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000494:pharmacology*; D034381:Hearing Loss / Q000473:pathology / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D016877:Oxidants / Q000633:toxicity; D030421:Peroxynitrous Acid / Q000633:toxicity; D051381:Rats; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
chemical_list: D000975:Antioxidants; D016877:Oxidants; D030421:Peroxynitrous Acid; D003545:Cysteine