Accumulation of 4-hydroxynonenal-modified proteins in hippocampal CA1 pyramidal neurons precedes delayed neuronal damage in the gerbil brain.
It has been proposed that reactive oxygen species and lipid peroxidation have a role in the delayed neuronal death of pyramidal cells in the CA1 region. To explore the in situ localization and serial changes of 4-hydroxy-2-nonenal-modified proteins, which are major products of membrane peroxidation, we used immunohistochemistry of the gerbil hippocampus after transient forebrain ischemia with or without preconditioning ischemia. The normal gerbil hippocampus showed weak immunoreactivity for 4-hydroxy-2-nonenal-modified proteins in the cytoplasm of CA1 pyramidal cells. 4-hydroxy-2-nonenal immunoreactivity showed no marked changes after preconditioning ischemia. In the early period after ischemia and reperfusion, there was a transient increase of nuclear 4-hydroxy-2-nonenal immunoreactivity in CA1 pyramidal neurons. In contrast, cytoplasmic immunoreactivity transiently disappeared during same period and then increased markedly from 8h to seven days. One week after ischemia, 4-hydroxy-2-nonenal immunoreactivity was observed within reactive astrocytes in the CA1 region. Early nuclear accumulation of 4-hydroxy-2-nonenal in CA1 neurons may indicate a possible role in signal transduction between the nucleus and cytoplasm/mitochondria, while delayed accumulation of 4-hydroxy-2-nonenal-modified proteins in the cytoplasm may be related to mitochondrial damage. We conclude that 4-hydroxy-2-nonenal may be a key mediator of the oxidative stress-induced neuronal signaling pathway and may have an important role in modifying delayed neuronal death.
Urabe
T
T
Department of Neurology, Juntendo University School of Medicine, 113-0033, Tokyo, Japan. t_urabe@med.juntendo.ac.jp
Yamasaki
Y
Y
Hattori
N
N
Yoshikawa
M
M
Uchida
K
K
Mizuno
Y
Y
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D005849:Gerbillinae; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D017966:Pyramidal Cells / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000447:Aldehydes; C027576:4-hydroxy-2-nonenal