Regulation of mGluR1 on the Expression of PKC and NMDAR in Aluminum-Exposed PC12 Cells

Abstract

Aluminum demonstrates clear neurotoxicity and can cause Alzheimer’s disease (AD)-like symptoms, including cognitive impairment. One toxic effect of aluminum is a decrease in synaptic plasticity, but the specific mechanism remains unclear. In this study, PC12 cells were treated with Al(mal)3 to construct a toxic cell model. (S)-3,5-Dihydroxyphenylglycine (DHPG), α-methyl-4-carboxyphenylglycine (MCPG), and mGluR1-siRNA were used to interfere with the expression of metabotropic glutamate receptor subtype 1 (mGluR1). Polymerase chain reaction and western blotting were used to investigate the expression of mGluR1, protein kinase C (PKC), and N-methyl-D-aspartate receptor (NMDAR) subunits. ELISA was used to detect PKC enzyme activity. In PC12 cells, mRNA and protein expressions of PKC and NMDAR subunits were inhibited by Al(mal)3. Aluminum may further regulate the expression of NMDAR1 and NMDAR2B through mGluR1 to regulate PKC enzyme activity, thereby affecting learning and memory functions. Furthermore, the results implied that the mGluR1-PKC-NMDAR signaling pathway may predominately involve positive regulation. These findings provide new targets for studying the neurotoxic mechanism of aluminum.

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Abbreviations

Al(mal)3 :

Aluminum maltol

mGluR1:

Metabolic glutamate receptor 1

PKC:

Protein kinase C

NMDAR:

N-methyl-D-aspartic acid receptor

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Acknowledgments

We sincerely thank colleagues for their help and work on the research.

Funding

This work was supported by the National Natural Science Foundation of China [Nos. 81430078, 81872599].

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Correspondence to Qiao Niu.

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He, C., Zhao, X., Li, H. et al. Regulation of mGluR1 on the Expression of PKC and NMDAR in Aluminum-Exposed PC12 Cells. Neurotox Res (2021). https://doi.org/10.1007/s12640-020-00319-5

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Keywords

  • Aluminum
  • Synaptic plasticity
  • Metabolic glutamate receptor 1
  • Protein kinase C
  • N-methyl-D-aspartic acid receptor