Lead exposure and tau hyperphosphorylation: An in vitro study

The presence of fibrillary lesions, which are mainly composed of the microtubule associated protein tau (MAPT) in neurons, has gained immense recognition due to their presence in numerous neurodegenerative diseases, including Alzheimer's disease (AD). Dysregulation of tau is related with its altered site specific phosphorylation which is followed by tau polymerization, neuronal dysfunction and death. Previous reports by us suggest that molecular alterations favor abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates and rodents with past exposure to lead (Pb). Here we report the involvement of Pb-induced alterations in tau and hyperphosphorylation of tau in differentiated Human Neuroblastoma SH-SY5Y cells exposed to a series of Pb concentrations (5-100 mu M) for 48 h. These cells were analyzed for the protein expression of total tau, site-specific tau hyperphosphorylation, cyclin dependent kinase 5 (CDK5) and p35/p25 at selected time points (24144 h), after Pb exposure had ceased. Western blot analysis revealed aberrant tau levels as well as site specific tau hyperphosphorylation accompanied by elevated CDK5 levels and altered protein ratio of p35/p25 particularly at 72 and 144 h. These changes provide additional evidence that neurodegenerative events are subject to environmental influences. (C) 2017 Elsevier B.V. All rights reserved.