Significant contribution of autophagy in mitigating cytotoxicity of gadolinium ions
| Autor: | Masako Kiyono, Yuka Ohshiro, Yasukazu Takanezawa, Tomoya Kusaka, Shimpei Uraguchi, Ryosuke Nakamura |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell Survival Biophysics chemistry.chemical_element Gadolinium Pharmacology Calcium Biochemistry Cell Line Mice 03 medical and health sciences 0302 clinical medicine Chloroquine Autophagy medicine Animals Humans RNA Messenger Viability assay Cytotoxicity Molecular Biology Ions Kidney Cell Death HEK 293 cells Cell Biology Endoplasmic Reticulum Stress 030104 developmental biology medicine.anatomical_structure chemistry Cytoprotection 030220 oncology & carcinogenesis Toxicity lipids (amino acids peptides and proteins) Transcription Factor CHOP medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 526:206-212 |
| ISSN: | 0006-291X |
| Popis: | Gadolinium-based contrast agents (GBCAs) are widely used in clinical magnetic resonance imaging (MRI). Free gadolinium ions (Gd3+) released from GBCAs potentially increase the risk of GBCA-related toxicity. However, the cellular responses to Gd3+ and the underlying mechanisms responsible for protection against Gd3+ remain poorly understood. Recently, autophagy has been considered a cell survival mechanism against various toxic metals. Here, we investigated the relationship between Gd3+ and autophagy, as well as the effect of autophagy inhibition on the survival of cells exposed to Gd3+. We found that the increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, a marker protein of autophagy, in Gd3+-exposed human embryonic kidney 293 (HEK293) cells. Moreover, we found a greater accumulation of LC3-II after exposure to an autophagy inhibitor, chloroquine (CQ), combined with Gd3+ than that after exposure to CQ alone, suggesting that Gd3+ activated autophagy in HEK293 cells. Furthermore, we found that Gd3+ reduced cell viability, which was more pronounced after CQ treatment. Our findings indicated that autophagy exerted a cytoprotective effect against Gd3+ toxicity, suggesting a potential link between autophagy and GBCA-associated adverse events. |
| Databáze: | OpenAIRE |
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