Up-regulation of cDK5/p35 by oxidative stress in human neuroblastoma IMR-32 cells.
Cdk5, a member of the cyclin-dependent kinase (cdk) family, is predominantly active in neurons, where its activity is tightly regulated by the binding of its neuronal activators p35 and p39. Cdk5 is implicated in regulating the proper neuronal function; a deregulation of cdk5 has been found associated with Alzheimer's disease and amyotrophic lateral sclerosis. As oxidative stress products have been seen co-localized with pathological hallmarks of neurodegenerative diseases, we studied the effect of oxidative stress on the cdk5 enzyme in human neuroblastoma IMR-32 cells. We evaluated the effects of 4-hydroxynonenal and Ascorbate plus FeSO(4) on cdk5 activity and on the expression of cdk5 and p35 proteins. We report here that oxidative stress stimulates cdk5 activity and induces an upregulation of its regulatory and catalytic subunit expression in IMR-32 vital cells, showing that the cdk5 enzyme is involved in the signaling pathway activated by oxidative stress.
Strocchi
Paola
P
Department of Pharmacology, University of Bologna, Bologna, Italy. strocchi@biocfarm.unibo.it
Pession
Annalisa
A
Dozza
Barbara
B
D000447:Aldehydes / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D002470:Cell Survival; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D008858:Microscopy, Phase-Contrast; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000447:Aldehydes; C108298:Cdk5 activator p39; D005296:Ferrous Compounds; D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); C020748:ferrous sulfate; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases; C027576:4-hydroxy-2-nonenal