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Expression of the hyperphosphorylated tau attenuates ER stress-induced apoptosis with upregulation of unfolded protein response

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Abstract

The neural dysfunction in Alzheimer’s disease (AD) could arise from endoplasmic reticulum (ER) stress and deficits of the unfolded protein response (UPR). To explore whether tau hyperphosphorylation, a hallmark of AD brain pathologies, plays a role in ER stress-induced alterations of cell viability, we established cell lines with stable expression of human tau (HEK293/tau) or the vector (HEK293/vec) and treated the cells with thapsigargin (TG), an ER stress inducer. We observed that the HEK293/tau cells were more resistant than the HEK293/vec cells to the TG-induced apoptosis, importantly, a time dependent increase of tau phosphorylation at Thr205 and Thr231 sites was positively correlated with the inhibition of apoptosis. We also observed that expression of tau upregulated phosphorylation of PERK, eIF2 and IRE1 with an increased cleavage of ATF6 and ATF4. The potentiation of UPR was also detected in HEK293/tau cells treated with other ER stress inducers, including staurosporine, camptothecin and hydrogen peroxide, in which a suppressed apoptosis was also shown. Our data suggest that tau hyperphosphorylation could attenuate the ER stress-induced apoptosis with the mechanism involving upregulation of UPR system.

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Acknowledgments

This work was supported in part by grants from National Natural Science Foundation of China (30971204, 30871035), a grant from Education Ministry of China (NCET050650), and a grant from Alzheimer’s Association (IIRG09133433).

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  1. Xin-An Liu

    Present address: Department of Neuroscience, The Scripps Research Institute, 33458, Jupiter, FL, USA

Authors and Affiliations

  1. Pathophysiology Department, Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China

    Xin-An Liu, Jie Song, Qian Jiang, Qun Wang, Qing Tian & Jian-Zhi Wang

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  1. Xin-An Liu
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  2. Jie Song
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  3. Qian Jiang
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Correspondence to Qing Tian or Jian-Zhi Wang.

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Liu, XA., Song, J., Jiang, Q. et al. Expression of the hyperphosphorylated tau attenuates ER stress-induced apoptosis with upregulation of unfolded protein response. Apoptosis 17, 1039–1049 (2012). https://doi.org/10.1007/s10495-012-0744-z

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