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Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+

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Abstract

Gadolinium (Gd) and its complexes are utilized widely in industrial and clinical diagnoses. As a rare earth metal ion, free gadolinium (Gd3+) in the human body poses neurotoxic risks during its in vivo release and retention. In the central nervous system, astrocytes play a pivotal role in processing toxic metal ions. The present study evaluates the effects of Gd on cellular calcium homeostasis, a common mechanism that causes cell death, and on unfolded protein responses (UPRs), a mechanism for cell survival in response to toxic stimuli in mammalian cells. The experimental results indicate that the influx of extracellular Ca2+ increases greatly after the exposure of astrocytes to Gd; however, no cell deaths were observed. Further evidence suggests the up-regulated expression of the endoplasmic reticulum (ER)-resident chaperone protein GRP78 by ER stress-mediated signal transductions, specifically the activation of ATF6, eIF2a, and IRE1. These results suggest that Gd promotes Ca2+ influx, thus triggering UPRs, which can be closely associated to the resistance of astrocytes to Gd-induced cytotoxicity.

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Acknowledgments

This work was supported by the NNSFC (Grant Nos. 20901005 and 20637010) and the Research Fund for the Doctoral Program of Higher Education (No. 200800011056).

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Authors and Affiliations

  1. State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China

    Xu-Dong Feng, Qing Xia, Lan Yuan, Hai-Feng Huang, Xiao-Da Yang & Kui Wang

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  1. Xu-Dong Feng
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  2. Qing Xia
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  3. Lan Yuan
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Correspondence to Qing Xia or Xiao-Da Yang.

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Xu-Dong Feng and Qing Xia contribute equally to this paper.

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Feng, XD., Xia, Q., Yuan, L. et al. Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+ . Cell Biol Toxicol 27, 1–12 (2011). https://doi.org/10.1007/s10565-010-9166-2

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  • DOI: https://doi.org/10.1007/s10565-010-9166-2

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