Neurobiology of Disease Essential Role of Cytoplasmic cdk5 and Prx2 in Multiple Ischemic Injury Models, In Vivo
نویسندگان
چکیده
Juliet Rashidian,1 Maxime W. Rousseaux,1 Katerina Venderova,1 Dianbo Qu,1 Steve M. Callaghan,1 Maryam Phillips,1 Ross J. Bland,2 Matthew J. During,3,4 Zixu Mao,5 Ruth S. Slack,1 and David S. Park1 1Neuroscience Group, Ottawa Health Research Institute, Ottawa, Ontario K1H 8M5, Canada, 2Neurologix, Fort Lee, New Jersey 07024, 3Department of Molecular Medicine and Pathology, University of Auckland, 92019 Auckland, New Zealand, 4Departement of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, College of Medicine, Columbus, Ohio 43210-1239, and 5Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322
منابع مشابه
Essential role of cytoplasmic cdk5 and Prx2 in multiple ischemic injury models, in vivo.
Recent evidence suggests that abnormal activation of cyclin-dependent kinase 5 (cdk5) is a critical prodeath signal in stroke. However, the mechanism(s) by which cdk5 promotes death is unclear. Complicating the role of cdk5 are the observations that cdk5 can exist in multiple cellular regions and possess both prosurvival and prodeath characteristics. In particular, the critical role of cytoplas...
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We reported previously that calpain-mediated Cdk5 activation is critical for mitochondrial toxin-induced dopaminergic death. Here, we report a target that mediates this loss. Prx2, an antioxidant enzyme, binds Cdk5/p35. Prx2 is phosphorylated at T89 in neurons treated with MPP+ and/or MPTP in animals in a calpain/Cdk5/p35-dependent manner. This phosphorylation reduces Prx2 peroxidase activity. ...
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Cyclin-dependent kinase 5(CDK5) in complex with its activator, p35 (protein of 35 kDa), is essential for early neurodevelopment in mammals. However, endogenous cleavage of p35 to p25 is associated with neuron death and neurodegenerative disease. Here we show that a peptide (p10') encoding the N-terminal domain of p35 protects against CDK5/p25-induced toxicity in neurons. p10' also prevented the...
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Objective(s): In the present study, we investigated the effect of ischemic preconditioning (IPC) on c-myb immunoreactivity as well as neuronal damage/death after a subsequent lethal transient ischemia in gerbils. Materials and Methods: IPC was subjected to a 2 min sublethal ischemia and a lethal transient ischemia was given 5 min transient ischemia. The animals in all of the groups were given ...
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