Kainic acid-induced oxidative injury is attenuated by hypoxic preconditioning.
Female Wistar rats were subjected to 380 mmHg in an altitude chamber for 15 h/day for 28 days. Hypoxic preconditioning attenuated kainic acid (KA)-induced oxidative injury, including KA-elevated lipid peroxidation and neuronal loss in rat hippocampus. Furthermore, KA-induced translocation of cytochrome c and apoptosis-inducing factor from mitochondria to cytosol was attenuated in the hypoxic rats. In addition, hypoxic preconditioning attenuated the KA-induced reduction in glutathione content and superoxide dismutase as well as KA-induced increase in glutathione peroxidase. Although local infusion of KA increased hippocampal NF-kappaB binding activity in the normoxic rat, hypoxia further enhanced KA-elevated NF-kappaB binding activity. Moreover, hypoxic preconditioning potentiated the KA-induced increase in Bcl-2 level in the lesioned hippocampus. Our data suggest that hypoxic preconditioning exerts its neuroprotection of KA-induced oxidative injury via enhancing NF-kappaB activation, upregulating the antioxidative defense system, and attenuating the apoptotic process.
Wang
Cheng-Hao
CH
Department of Physiology, National Yang-Ming University, Taipei, Taiwan.
Chang
Anyu
A
Tsai
May-Jywan
MJ
Cheng
Henrich
H
Liao
Li-Ping
LP
Lin
Anya Maan-Yuh
AM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006400:Hematocrit; D000860:Hypoxia / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY
D000975:Antioxidants; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D007608:Kainic Acid