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Increase of glycogen storage by sodium arsenite in rat cortical astrocytes through glycogen synthase activation and its association to toxicity

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Abstract

Objective

The present study aimed primarily to evaluate the effect of sodium arsenite exposure on glucose metabolism includes glycogen accumulation on rat cortical astrocytes. Furthermore, cell death analysis was concurrently done to determine the toxic effect of sodium arsenite on astrocytes.

Methods

Rat cortical astrocytes derived from the cerebral cortices of neonatal Wistar rats were treated with sodium arsenite for 24 h. Glucose metabolism was evaluated by determining glucose uptake and glycogen accumulation using glucose uptake kit, and periodic acid–Schiff staining and transmission electron microscopy, respectively. Glycogen synthase (GS) and glycogen synthase kinase-3 (GSK3) were detected by Western blotting. The cell death analysis was assessed by propidium iodide staining.

Results

Sodium arsenite exposure at 25 μM for 24 h significantly increased glucose uptake and glycogen content in rat cortical astrocytes. Sodium arsenite exposure significantly increased GS expression but decreased a ratio of GS phosphorylation at serine 641 (inactive) to GS, suggesting that there may be an increase in activity of GS. Moreover, sodium arsenite caused an increase in inactive serine phosphorylation of GSK3, a kinase that phosphorylates and inhibits GS. These results suggested that sodium arsenite increased glycogen synthesis through GS activation mediated by inhibition of GSK3. On the other hand, sodium arsenite exposure at 25 μM caused some degree of cellular damage and a slight increase in cell death in rat astrocytes.

Conclusion

Sodium arsenite increased glycogen accumulation through GS activation and caused cell death in rat cortical astrocytes. These observations implicate that the enhancement of glycogen in rat astrocytes by sodium arsenite may be related to its toxicity. Hence, alteration of astrocyte glycogen metabolism may play a role in arsenic toxicity in the brain.

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Acknowledgements

This work is supported by grants from the Chulabhorn Research Institute, and the Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Higher Education, Science, Research and Innovation, Thailand. We thank Dr. James M. Dubbs for kindly proof-reading the manuscript.

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Authors and Affiliations

  1. Laboratory of Pharmacology, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok, 10210, Thailand

    Selapoom Pairor, Benjaporn Homkajorn, Sumitra Suntararuks, Piyajit Watcharasit & Jutamaad Satayavivad

  2. Chulabhorn Graduate Institute, 54 Kamphaeng Phet 6 Road, Bangkok, 10210, Thailand

    Selapoom Pairor, Piyajit Watcharasit & Jutamaad Satayavivad

  3. Department of Anatomy, Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkok, 10700, Thailand

    Apichaya Niyomchan

  4. Center of Excellence On Environmental Health and Toxicology (EHT), Ministry of Higher Education, Science, Research and Innovation, 272 Rama 6 Road, Bangkok, 10400, Thailand

    Piyajit Watcharasit & Jutamaad Satayavivad

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  1. Selapoom Pairor
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Correspondence to Piyajit Watcharasit.

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Selapoom Pairor, Benjaporn Homkajorn, Apichaya Niyomchan, Sumitra Suntararuks, Piyajit Watcharasit and Jutamaad Satayavivad declare that they have no conflict of interest.

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Pairor, S., Homkajorn, B., Niyomchan, A. et al. Increase of glycogen storage by sodium arsenite in rat cortical astrocytes through glycogen synthase activation and its association to toxicity. Toxicol. Environ. Health Sci. 13, 153–163 (2021). https://doi.org/10.1007/s13530-021-00094-6

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