Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells.
Recently apoptotic markers have been found in Alzheimer's Disease (AD) brain. To investigate the relation between tau phosphorylation and apoptosis, immunocytochemistry of AT8 (indicating the degree of phosphorylation at the tau Ser202/Thr205 site) was quantitatively determined the degree of tau phosphorylation at the Ser202 site was monitored during neuronal apoptosis in differentiated PC12 cells after nerve growth factor (NGF) deprivation. During this programmed cell death a prominent retraction of neurites took place that was associated with a clear increase in the level of AT8 signalaberrant phosphorylated tau at the Ser202 site. The broad spectrum kinase inhibitor staurosporine attenuated both this increase in tau phosphorylation, neurite retraction, and apoptosis. We suggest that at some point during programmed cell death, kinases with tau as substrate become activated and that the resulting loss of cytoskeletal integrity leads to neurite instability.
Nuydens
R
R
Department of Cell Physiology, Janssen Research Foundation, Beerse, Belgium.
Dispersyn
G
G
de Jong
M
M
van den Kieboom
G
G
Borgers
M
M
Geerts
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D048429:Cell Size; D003599:Cytoskeleton / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D007150:Immunohistochemistry; D008858:Microscopy, Phase-Contrast; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D000939:Epitopes; D009414:Nerve Growth Factors; D016875:tau Proteins; D017346:Protein Serine-Threonine Kinases; D019311:Staurosporine