Poly(ADP-ribose) polymerase-1 is involved in the neuronal death induced by quinolinic acid in rats |
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| Authors: | Perla Deyanira Maldonado,Marí a Elena Chá nez-Cá rdenas,Diana Barrera,Juana Villeda-Herná ndez,Abel Santamarí a,José Pedraza-Chaverrí |
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| Affiliation: | 1. Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México, D.F. 14269, Mexico;2. Facultad de Medicina, Departamento de Farmacología, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico;3. Laboratorio de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México, D.F. 14269, Mexico;4. Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México, D.F. 14269, Mexico;5. Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico |
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| Abstract: | Reactive oxygen and nitrogen species formation leads to DNA damage in animals treated with quinolinic acid. Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in the DNA base excision repair system. Its overactivation promotes cellular energy deficit and necrosis. Here, we evaluated the effect of PJ-34, a potent inhibitor of PARP-1, on the neuronal damage induced by quinolinic acid. Animals were administered with PJ-34 (10 mg/kg, i.p.), 1 h before and 1 h after a striatal infusion of 1 μl of quinolinic acid (240 nmol). PJ-34 clearly attenuated the circling behavior produced by quinolinic acid and completely prevented the histological damage induced by the toxin. The protective effect of PJ-34 suggests that PARP-1 activation is playing an active role in the neuronal death induced by quinolinic acid. |
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| Keywords: | PJ-34 Quinolinic acid Poly(ADP-ribose) polymerase |
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