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The Palmitoylation/Depalmitoylation Cycle is Involved in the Inhibition of AMPA Receptor Trafficking Induced by Aluminum In Vitro

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Abstract

To study the effect of the palmitoylation/depalmitoylation cycle on the inhibition of ɑ-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptor trafficking induced by aluminum (Al) in vitro. Five different doses of aluminum-maltolate complex (Al(mal)3) were administered to rat adrenal pheochromocytoma cells (PC12 cells) for three exposure time durations, and the cell activity was measured by the CCK-8 method to obtain the optimal doses and time of Al(mal)3 exposure. Following Al(mal)3 exposure, membrane protein (M) and total protein (T) were extracted. The expression levels of GluR1 and GluR2, which are AMPA receptor subunits, were determined by Western blot analysis, and the levels with respect to membrane and total protein were calculated. The ratio of membrane protein to total protein (M/T) was used to measure the rate of AMPA receptor transport. The palmitoylation levels of GluR1 and GluR2 were detected by immunoprecipitation-acyl-biotin exchange (IP-ABE) assay. Western blotting was performed to detect the protein expression of acyltransferase (zDHHC3) and palmitoyl protein thioesterase 1 (PPT1). Following depalmitoylation inhibitor (palmostatin B) treatment of PC12 cells, the effect of aluminum on AMPA receptor trafficking was detected through the aforementioned methods. With increasing Al(mal)3 doses administered to PC12 cells, a gradual decrease in the trafficking of AMPA receptor subunits GluR1 and GluR2 and in the palmitoylation levels of GluR1 and GluR2 was found; the expression of zDHHC3 was decreased; and the expression of PPT1 was increased. In addition, palmostatin B reduced the effects of Al(mal)3 on AMPA receptor palmitoylation and trafficking. Al can inhibit the trafficking of the AMPA receptor in vitro, and a decrease in the palmitoylation level of the AMPA receptor may be a mechanism of Al action. The palmitoylation/depalmitoylation cycle of the AMPA receptor is influenced by Al through the actions of zDHHC3 and PPT1.

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Acknowledgements

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

Funding

This research was financially supported by the Research Project Supported by Shanxi Scholarship Council of China. [No.2021–083].

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Authors and Affiliations

  1. Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China

    Jing Song, Ting Gao, Wenjing Li, Chunman Yuan, Jiarui Hao & Xinyu Xia

  2. Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, Taiyuan, China

    Jing Song

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  1. Jing Song
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  2. Ting Gao
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  3. Wenjing Li
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  4. Chunman Yuan
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Correspondence to Jing Song.

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Song, J., Gao, T., Li, W. et al. The Palmitoylation/Depalmitoylation Cycle is Involved in the Inhibition of AMPA Receptor Trafficking Induced by Aluminum In Vitro. Biol Trace Elem Res 201, 1398–1406 (2023). https://doi.org/10.1007/s12011-022-03234-2

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