mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B,Journal of Agricultural and Food Chemistry

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mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-01 , DOI: 10.1021/acs.jafc.4c05702
Jiaqiao Zhu _{1,

2,

3} , Zhonggui Gong _{1,

4,

5} , Xueru Wang _{1,

2,

3} , Kanglei Zhang _{1,

2,

3} , Yonggang Ma _{1,

2,

3} , Hui Zou _{1,

2,

3} , Ruilong Song _{1,

2,

3} , Hongyan Zhao _{1,

2,

3} , Zongping Liu _{1,

2,

3} , Wenxuan Dong _{1,

6}

Affiliation

The potential threat of cadmium (Cd)-induced acute kidney injury (AKI) is increasing. In this study, our primary goal was to investigate the individual roles played by mTOR complexes, specifically mTORC1 and mTORC2, in Cd-induced apoptosis in mouse kidney cells. We constructed a mouse model with specific deletion of Raptor/Rictor renal cells. Inhibitors and activators of mTORC1 or mTORC2 were also applied. The effects of protein kinase B (AKT) activation and autophagy were studied. Both mTORC1 and mTORC2 were found to mediate the antiapoptotic mechanism of renal cells by regulating the AKT activity. Inhibition of mTORC1 or mTORC2 exacerbated Cd-induced kidney cell apoptosis, suggesting that both proteins exert antiapoptotic effects under Cd exposure. We further found that the AKT activation plays a key role in mTORC1/TORC2-mediated antiapoptosis, protecting Cd-exposed kidney cells from apoptosis. We also found that mTOR activators inhibited excessive autophagy, alleviated apoptosis, and promoted cell survival. These findings provide new insights into the regulatory mechanisms of mTOR in renal diseases and provide a theoretical basis for the development of novel therapeutic strategies to treat renal injury.

中文翻译：

mTORC1 和 mTORC2 通过调节蛋白激酶 B 共同防止镉诱导的肾小管上皮细胞凋亡和急性肾损伤

镉（Cd）诱导的急性肾损伤（AKI）的潜在威胁正在增加。在这项研究中，我们的主要目标是研究 mTOR 复合物（特别是 mTORC1 和 mTORC2）在 Cd 诱导的小鼠肾细胞凋亡中发挥的个体作用。我们构建了一个具有 Raptor/Rictor 肾细胞特异性缺失的小鼠模型。还应用了 mTORC1 或 mTORC2 的抑制剂和激活剂。研究了蛋白激酶 B （AKT）激活和自噬的影响。发现 mTORC1 和 mTORC2 都通过调节 AKT 活性介导肾细胞的抗凋亡机制。mTORC1 或 mTORC2 的抑制加剧了 Cd 诱导的肾细胞凋亡，表明这两种蛋白在 Cd 暴露下都发挥抗凋亡作用。我们进一步发现 AKT 激活在 mTORC1/TORC2 介导的抗凋亡中起关键作用，保护 Cd 暴露的肾细胞免于凋亡。我们还发现 mTOR 激活剂抑制过度自噬，减轻细胞凋亡，促进细胞存活。这些发现为 mTOR 在肾脏疾病中的调控机制提供了新的见解，并为开发治疗肾损伤的新型治疗策略提供了理论基础。

更新日期：2024-09-01

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