Involvement of nitric oxide and free radical (O2-) in neuronal injury induced by deprivation of oxygen and glucose in vitro.
Nitrix oxide (NO) is a free radical that has been recently proposed as a messenger molecule in the central nervous system. Since its involvement in glutamate neurotoxicity in vitro has been recently reported, using rat cortical cultures, we tested the hypothesis that NO also plays a role in neuronal injury induced by deprivation of oxygen and glucose. About 80-90% of neurons were killed in less than 12 h after a 4-6 h period of oxygen and glucose deprivation. N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxidase synthase (NOS), significantly ameliorated this neuronal injury in a dose dependent manner. Since it has been suggested that NO is inactivated in a short time period by interaction with superoxide anions (O2-), which are generated during ischemia-reperfusion in vivo, we further evaluated the effect of superoxide dismutase (SOD) on neuronal injury in this test system. SOD failed, however, to protect against neuronal death. Furthermore, concomitant addition of SOD and L-NNA rather reduced the beneficial effects of L-NNA. Our results suggest therefore that NO, at least in part, mediates neuronal injury secondary to deprivation of oxygen and glucose in vitro and that superoxide anions may have a protective role by inactivating NO.
Ikeda
J
J
Department of Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.
Ma
L
L
Morita
I
I
Murota
S
S
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology*; D046508:Culture Techniques; D005609:Free Radicals; D009410:Nerve Degeneration / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
D001786:Blood Glucose; D005609:Free Radicals; D017382:Reactive Oxygen Species; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000594:Amino Acid Oxidoreductases