NDLI: N-methyl-D-aspartate Receptors are Involved in the Quinolinic Acid, but not in the Malonate Pro-oxidative Activity in vitro

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N-methyl-D-aspartate Receptors are Involved in the Quinolinic Acid, but not in the Malonate Pro-oxidative Activity in vitro

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N-methyl-D-aspartate Receptors are Involved in the Quinolinic Acid, but not in the Malonate Pro-oxidative Activity in vitro

Content Provider	Springer Nature Link
Author	Puntel, Robson Luiz gueira, Cristina Wayne Rocha, João Batista Teixeira
Copyright Year	2005
Abstract	Oxidative stress plays a significant role in the neurotoxicity of a variety of agents that interact with the N-methyl-D-aspartate (NMDA) receptors. Here we investigated in a comparative way the pro-oxidative effects of quinolinic acid (QA) and malonate, two neurotoxic substances that act through distinct primary molecular mechanisms on the production of thiobarbituric acid reactive species (TBARS) by brain homogenates. In fact, QA is thought to activate directly the NMDA receptor, whereas malonate seems to act primarily by inhibiting oxidative metabolism. The malonate-induced TBARS formation was not modified by cyanide (CN$^{−}$) or 2,4-dinitrophenol. MK-801 did not reduce basal or malonate induced-TBARS production in fresh tissues preparations. However, in heat-treated preparations a significant effect of MK-801 against basal TBARS production was observed, but not on the malonate induced-TBARS production. QA induced-TBARS production was significantly prevented by MK-801 either in fresh or heat-treated preparations. The antioxidant effect of MK-801 on basal and QA-induced TBARS production increased as the temperatures used to treat S1 were increased. Succinate dehydrogenase (SDH) was inhibited by malonate but not by QA. Malonate was able to chelate iron(II) and the malonate-iron complex(es) is(are) active as measured by its(their) activity on deoxyribose degradation assay. These findings indicate that direct interactions of malonate with NMDA receptors are not involved in malonate pro-oxidative activity in vitro. QA pro-oxidative activity in vitro was related, at least in part, to its capability in stimulate NMDA receptors. Taken together, these findings indicated that malonate pro-oxidative activity in vitro could be attributed to its capability of changing the ratio Fe$^{2+}$/ Fe$^{3+}$, which is essential to TBARS production.
Starting Page	417
Ending Page	424
Page Count	8
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	30
Issue Number	3
e-ISSN	15736903
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	2005-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Iron; malonate NMDA receptors pro-oxidant quinolinic acid Neurosciences Neurology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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