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Luteolin Reduces Zinc-Induced Tau Phosphorylation at Ser262/356 in an ROS-Dependent Manner in SH-SY5Y Cells

Biological Trace Element Research volume 149, pages 273–279 (2012)Cite this article

Abstract

In brain, excess zinc alters the metabolism of amyloid precursor protein, leading to β-amyloid protein deposition, one of the hallmarks of Alzheimer’s disease (AD) pathology. Recently, it has been reported that zinc accelerates in vitro tau fibrillization, another hallmark of AD. In the current study, we examined the effect of high-concentration zinc on tau phosphorylation in human neuroblastoma SH-SY5Y cells. We found that incubation of cells with zinc resulted in abnormal tau phosphorylation at Ser262/356. Moreover, the current study has investigated whether luteolin (Lu), a bioflavonoid, could decrease zinc-induced tau hyperphosphorylation and its underlying mechanisms. Using Western blot and protein phosphatase activity assay, activities of tau kinases and phosphatase were investigated. Our data suggest (1) that zinc induces tau hyperphosphorylation at Ser262/356 epitope and (2) that Lu efficiently attenuates zinc-induced tau hyperphosphorylation through not only its antioxidant action but also its regulation of the phosphorylation/dephosphorylation system.

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Abbreviations

AD:

Alzheimer’s disease

CaMKII:

Calcium/calmodulin-dependent protein kinase II

ERK1/2:

Extracellular signal-regulated kinases 1 and 2

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GSH:

Reduced glutathione

GSK3β:

Glycogen synthase kinase 3β

H2O2 :

Hydrogen peroxide

Lu:

Luteolin

mTOR:

Mammalian target of rapamycin

NFTs:

Neurofibrillary tangles

OA:

Okadaic acid

p70S6K:

70-kDa Ribosomal protein S6 kinase

PP2A:

Protein phosphatase 2A

Rapa:

Rapamycin

ROS:

Reactive oxygen species

SH-SY5Y:

Human SH-SY5Y neuroblastoma cells

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Acknowledgements

This work was supported by Foundation of Doctor Scientific Research of Nanchang Hangkong University, Foundation of State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center (no. SMFA10B01), and National Natural Science Foundation of China (no. 30973686).

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Authors and Affiliations

  1. School of Physical Education, Nanchang Hangkong University, Nanchang, Jiangxi, 330063, China

    Futao Zhou, Shuangrong Chen & Jinping Xiong

  2. State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, 100094, China

    Yinghui Li & Lina Qu

Authors
  1. Futao Zhou
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  2. Shuangrong Chen
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  3. Jinping Xiong
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  4. Yinghui Li
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  5. Lina Qu
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Correspondence to Futao Zhou or Lina Qu.

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Zhou, F., Chen, S., Xiong, J. et al. Luteolin Reduces Zinc-Induced Tau Phosphorylation at Ser262/356 in an ROS-Dependent Manner in SH-SY5Y Cells. Biol Trace Elem Res 149, 273–279 (2012). https://doi.org/10.1007/s12011-012-9411-z

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  • DOI: https://doi.org/10.1007/s12011-012-9411-z

Keywords

  • Luteolin
  • Tau phosphorylation
  • Tau kinases
  • ROS