Vulnerability of neurons with mitochondrial dysfunction to oxidative stress is associated with down-regulation of thioredoxin.
In this study, we first developed an in vitro model of neuron with mitochondrial dysfunction, based on sodium azide (NaN(3))-induced inhibition of cytochrome c oxidase (complex IV) that is reduced in post-mortem AD brains, and then investigated the role of Trx expression in response of neurons with mitochondrial dysfunction to oxidative stress. We found that neurons treated with sub-threshold concentration (8mM) of NaN(3) have mitochondrial dysfunction and that thioredoxin (Trx) mRNA and protein level decreased in neurons with mitochondrial dysfunction though no significant change in the viability. When exposed to extracellular H(2)O(2), neurons with mitochondrial dysfunction were significantly more vulnerable than control neurons. Trx mRNA and protein levels in neurons with mitochondrial dysfunction decreased in a dose- and time-dependent manner (mRNA: 25-150 microM H(2)O(2) for 1h and 50 microM H(2)O(2) for 1-3h; protein: 25-150 microM H(2)O(2) for 1h and 50 microM H(2)O(2) for 1-4h), while those in control neurons had no significant changes (50-250 microM H(2)O(2) for 1h). The data implied that vulnerability of neurons with mitochondrial dysfunction to oxidative stress is associated with down-regulation of thioredoxin.
Gao
Jing
J
School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China. jinggao@ujs.edu.cn
Zhu
Zeng-Rong
ZR
Ding
Hong-Qun
HQ
Qian
Zhongming
Z
Zhu
Li
L
Ke
Ya
Y
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019810:Sodium Azide / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles; D013879:Thioredoxins / Q000096:biosynthesis*; D013997:Time Factors
D004791:Enzyme Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D013879:Thioredoxins; D012313:RNA; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV; C022616:thiazolyl blue