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牛磺酸通过调节自噬通量缓解镉诱导的肝毒性。

Taurine Alleviates Cadmium-Induced Hepatotoxicity by Regulating Autophagy Flux.

机构信息

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou 225009, China.

出版信息

Int J Mol Sci. 2023 Jan 7;24(2):1205. doi: 10.3390/ijms24021205.

Abstract

Our previous studies have confirmed that cadmium (Cd) exposure causes hepatotoxicity; it also induces autophagy and blocks the autophagy flux. Therefore, we hypothesized that Cd hepatotoxicity could be alleviated through nutritional intervention. Taurine (Tau) has various biological functions such as acting as an antioxidant, acting as an anti-inflammatory, and stabilizing cell membranes. In order to explore the protective effect and internal mechanism of Tau on Cd-induced hepatotoxicity, normal rat liver cell line BRL3A cells were treated with Cd alone or in combination with Tau to detect cell injury and autophagy-related indexes in this study. We found that Tau can alleviate Cd-induced cell-proliferation decline and morphological changes in the cell. In addition, Tau activates autophagy and alleviates the blockage of Cd-induced autophagy flux. In this process, lysosome acidification and degradation were enhanced, and autophagosomes were further fused with lysosomes. Then, we found that Tau alleviated autophagic flux block by promoting the transfer of membrane fusion proteins STX17 and SNAP29 to autophagosomes and the translocation of VAMP8 to lysosomes, which in turn attenuated the hepatocyte injury induced by Cd exposure. This will further reveal the hepatotoxicity mechanism of Cd and provide the theoretical basis for the prevention and treatment of Cd poisoning.

摘要

我们之前的研究已经证实,镉(Cd)暴露会导致肝毒性;它还会诱导自噬并阻断自噬流。因此,我们假设通过营养干预可以减轻 Cd 肝毒性。牛磺酸(Tau)具有多种生物学功能,如抗氧化、抗炎和稳定细胞膜。为了探索 Tau 对 Cd 诱导的肝毒性的保护作用及其内在机制,本研究用 Cd 单独或与 Tau 联合处理正常大鼠肝细胞系 BRL3A 细胞,检测细胞损伤和自噬相关指标。我们发现 Tau 可以减轻 Cd 诱导的细胞增殖下降和细胞形态变化。此外,Tau 激活自噬并减轻 Cd 诱导的自噬流阻断。在这个过程中,溶酶体酸化和降解增强,自噬体进一步与溶酶体融合。然后,我们发现 Tau 通过促进膜融合蛋白 STX17 和 SNAP29 向自噬体的转移以及 VAMP8 向溶酶体的易位,减轻 Cd 暴露引起的肝细胞损伤,从而减轻自噬流阻断。这将进一步揭示 Cd 的肝毒性机制,并为 Cd 中毒的预防和治疗提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f470/9861963/487238b4f433/ijms-24-01205-g001.jpg

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