Acute and long-term proteome changes induced by oxidative stress in the developing brain.
The developing mammalian brain experiences a period of rapid growth during which various otherwise innocuous environmental factors cause widespread apoptotic neuronal death. To gain insight into developmental events influenced by a premature exposure to high oxygen levels and identify proteins engaged in neurodegenerative and reparative processes, we analyzed mouse brain proteome changes at P7, P14 and P35 caused by an exposure to hyperoxia at P6. Changes detected in the brain proteome suggested that hyperoxia leads to oxidative stress and apoptotic neuronal death. These changes were consistent with results of histological and biochemical evaluation of the brains, which revealed widespread apoptotic neuronal death and increased levels of protein carbonyls. Furthermore, we detected changes in proteins involved in synaptic function, cell proliferation and formation of neuronal connections, suggesting interference of oxidative stress with these developmental events. These effects are age-dependent, as they did not occur in mice subjected to hyperoxia in adolescence.
Kaindl
A M
AM
Department of Pediatric Neurology, Charité, University Medical School, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. angela.kaindl@charite.de
Sifringer
M
M
Zabel
C
C
Nebrich
G
G
Wacker
M A
MA
Felderhoff-Mueser
U
U
Endesfelder
S
S
von der Hagen
M
M
Stefovska
V
V
Klose
J
J
Ikonomidou
C
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D000860:Hypoxia / Q000503:physiopathology; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics; D064231:Nestin; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000032:analysis / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D020543:Proteome / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000089622:Doublecortin Domain Proteins; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D009479:Neuropeptides; D011506:Proteins; D020543:Proteome; D012333:RNA, Messenger