title: Calpain activation is involved in acute manganese neurotoxicity in the rat striatum in vivo.
abstract: Manganese is essential for life, yet chronic exposure to this metal can cause a neurodegenerative disease named manganism that affects motor function. In the present study we have evaluated Mn neurotoxicity after its administration in the rat striatum. The participation of the calcium-dependent protease calpain and the apoptosis-related protease caspase-3, in Mn-induced cell death was monitored in the striatum and globus pallidus. Mn induced the activation of both proteases, although calpain activation seems to be an earlier event. Moreover, while the broad-spectrum caspase inhibitor QVD did not significantly prevent Mn-induced cell death, the specific calpain inhibitor MDL-28170 did. The role of NMDA glutamate receptors on calpain activity was also investigated; blockage of these receptors by MK-801 and memantine did not prevent calpain activation, nor Mn-induced cell death. Finally, studies in striatal homogenates suggest a direct activation of calpain by Mn ions. Altogether the present study suggests that additional mechanisms to excitotoxicity are involved in Mn-induced cell death, placing calpain as an important mediator of acute Mn neurotoxicity in vivo.
authors: Departamento de Química, Centro de Investigación y de Estudios Avanzados (Cinvestav), México DF, México. lilianaq@cinvestav.mx
authors: Liliana
authors: L
authors: Quintanar
authors: Teresa
authors: T
authors: Montiel
authors: Maripaz
authors: M
authors: Márquez
authors: Alejandra
authors: A
authors: González
authors: Lourdes
authors: L
authors: Massieu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D053148:Caspase 3; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005452:Fluoresceins; D005917:Globus Pallidus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008345:Manganese / Q000633:toxicity*; D020149:Manganese Poisoning / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009930:Organic Chemicals; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005452:Fluoresceins; D009419:Nerve Tissue Proteins; D009930:Organic Chemicals; C435731:fluoro jade; D008345:Manganese; D016291:Dizocilpine Maleate; D002154:Calpain; D053148:Caspase 3; D008559:Memantine