Mitochondrial peroxiredoxin-3 protects hippocampal neurons from excitotoxic injury in vivo.
Mitochondria are involved in excitotoxic damage of nerve cells. Following the breakdown of the calcium-buffering ability of mitochondria, mitochondrial calcium overload induces reactive oxygen species (ROS) bursts that produce free radicals and open permeability transition pores, ultimately leading to neuronal cell death. In the present study, we focused on a mitochondrial antioxidant protein, peroxiredoxin-3 (Prx-3), to investigate the mechanism by which toxic properties of ROS were up-regulated in mitochondria of damaged nerve cells. Immunohistochemical analysis revealed that Prx-3 protein exists in mitochondria of rat hippocampus, whereas we found a significant decrease in Prx-3 mRNA and protein levels associated with an increase in nitrated proteins in the rat hippocampus injured by microinjection of ibotenic acid. Furthermore, in vivo adenoviral gene transfer of Prx-3 completely inhibited protein nitration and markedly reduced gliosis, a post-neuronal cell death event. Since mitochondrial Prx-3 seems to be neuroprotective against oxidative insults, our findings suggest that Prx-3 up-regulation might be a useful novel approach for the management of neurodegenerative diseases.
Hattori
Fumiyuki
F
Daiichi Suntory Biomedical Research Co., Ltd, Shimamoto-cho, Mishima-gun, Osaka, Japan. Fumiyuki_Hattori@cpnet.med.keio.ac.jp
Murayama
Norihito
N
Noshita
Takafumi
T
Oikawa
Shinzo
S
D016475:3T3 Cells; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry; D016923:Cell Death / Q000187:drug effects; D018014:Gene Transfer Techniques; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007051:Ibotenic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008845:Microinjections; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D030421:Peroxynitrous Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics
D008164:Luminescent Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; C516116:Prdx3 protein, mouse; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D030421:Peroxynitrous Acid; D049452:Green Fluorescent Proteins; D007051:Ibotenic Acid; D010544:Peroxidases; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D001616:beta-Galactosidase