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钆喷酸葡胺诱导人角质形成细胞自噬和凋亡。

Gadodiamide Induced Autophagy and Apoptosis in Human Keratinocytes.

机构信息

Department of Diagnostic Radiology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.

School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan, R.O.C.

出版信息

In Vivo. 2022 Mar-Apr;36(2):603-609. doi: 10.21873/invivo.12743.

DOI:10.21873/invivo.12743
PMID:35241512
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8931910/
Abstract

BACKGROUND/AIM: Gadolinium has been reported to cause liver lobular necrosis and nephrogenic systemic fibrosis. However, its toxicity to the skin remains unknown. This study aimed to investigate the effect of a high dose of gadolinium-based contrast agent gadodiamide on the human keratinocyte HaCaT cell line.

MATERIALS AND METHODS

Cell viability was assessed using MTT assay, and autophagy was assessed using acridine orange and LysoTracker Red staining. Western blotting was performed to verify the changes in Bcl2 and Bax levels.

RESULTS

The viability of HaCaT cells was significantly suppressed after gadodiamide treatment. Interestingly, gadodiamide caused autophagic vacuoles, whereas the autophagy inhibitors 3-methyladenine and chloroquine significantly alleviated autophagic cell death. Simultaneously, gadodiamide induced apoptosis, which was reduced by caspase inhibitors. Gadodiamide also inhibited Bcl-2 expression and promoted Bax expression.

CONCLUSION

Gadodiamide induced both autophagy and apoptosis in HaCaT cells. Physicians should carefully assess the gadodiamide dosage used clinically.

摘要

背景/目的:钆剂已被报道可引起肝小叶坏死和肾源性系统性纤维化。然而,其对皮肤的毒性仍不清楚。本研究旨在探讨高剂量的基于钆的造影剂钆喷酸葡胺对人角质形成细胞 HaCaT 细胞系的影响。

材料和方法

通过 MTT 测定评估细胞活力,通过吖啶橙和 LysoTracker Red 染色评估自噬。通过 Western blot 验证 Bcl2 和 Bax 水平的变化。

结果

钆喷酸葡胺处理后 HaCaT 细胞活力明显受到抑制。有趣的是,钆喷酸葡胺引起自噬空泡,而自噬抑制剂 3-甲基腺嘌呤和氯喹可显著减轻自噬性细胞死亡。同时,钆喷酸葡胺诱导细胞凋亡,而 caspase 抑制剂可减少凋亡。钆喷酸葡胺还抑制 Bcl-2 的表达,促进 Bax 的表达。

结论

钆喷酸葡胺诱导 HaCaT 细胞发生自噬和凋亡。临床医生应仔细评估使用的钆喷酸葡胺剂量。