Bai Changcun, Tang Meng
School of Public Health, Bengbu Medical University, Bengbu 233000, PR China.
Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, Southeast University, Nanjing 210009, PR China.
Toxicology. 2025 Nov;517:154212. doi: 10.1016/j.tox.2025.154212. Epub 2025 Jun 4.
Previous study has shown that CdTe QDs exposure reduced ND7/23 cells activity and induced cell apoptosis in a time-dependent manner. The mitochondrial pathway was involved in CdTe QDs-induced ND7/23 cell apoptosis. The toxic effects at the subcellular level of ND7/23 cells after CdTe QDs exposure was still unclear. Whether the two classical mechanisms, endoplasmic reticulum stress and calcium ion imbalance, were involved in the subcellular structural and functional dysfunction of ND7/23 cells induced by CdTe QDs, and whether the Ca -calpain2 pathway played a significant role in the CdTe QDs-induced ND7/23 cell apoptosis remained to be validated. Therefore, this research focused on the study of CdTe QDs exposure-induced endoplasmic reticulum stress, organelle damage, and calcium homeostasis imbalance in ND7/23 cells. The apoptosis signaling pathway mediated by calpain2 and endoplasmic reticulum stress were also investigated. The results showed that exposure to 10 μM CdTe QDs for 0-24 h resulted in an increase in intracellular and mitochondrial Ca concentration, accompanied by swelling of the endoplasmic reticulum and mitochondria and loss of mitochondrial cristae. CdTe QDs exposure also led to an increase in the expression of endoplasmic reticulum stress-related Bip protein. CdTe QDs exposure also initiated the up-regulation of calpain2 and cleaved-caspase7 protein expression, as well as cleavage of caspase12 and PARP proteins in ND7/23 cells. Addition of the calcium chelator BAPTA-AM and the calpeptin 2 inhibitor calpeptin significantly inhibited CdTe QDs-induced apoptosis and reversed the expression of these proteins. This study confirmed that exposure to CdTe QDs triggered endoplasmic reticulum stress in ND7/23 cells, along with the activation of the calpain2-caspase12 signaling pathway, resulting in mitochondria-independent apoptosis.
先前的研究表明，暴露于碲化镉量子点会降低ND7/23细胞活性，并以时间依赖性方式诱导细胞凋亡。线粒体途径参与了碲化镉量子点诱导的ND7/23细胞凋亡。碲化镉量子点暴露后ND7/23细胞亚细胞水平的毒性作用仍不清楚。内质网应激和钙离子失衡这两种经典机制是否参与了碲化镉量子点诱导的ND7/23细胞亚细胞结构和功能障碍，以及Ca -钙蛋白酶2途径在碲化镉量子点诱导的ND7/23细胞凋亡中是否起重要作用仍有待验证。因此，本研究聚焦于碲化镉量子点暴露诱导的ND7/23细胞内质网应激、细胞器损伤和钙稳态失衡的研究。还研究了钙蛋白酶2和内质网应激介导的凋亡信号通路。结果表明，暴露于10μM碲化镉量子点0-24小时会导致细胞内和线粒体钙浓度增加，同时伴有内质网和线粒体肿胀以及线粒体嵴丢失。碲化镉量子点暴露还导致内质网应激相关Bip蛋白表达增加。碲化镉量子点暴露还引发了ND7/23细胞中钙蛋白酶2和裂解的半胱天冬酶7蛋白表达上调，以及半胱天冬酶12和PARP蛋白的裂解。添加钙螯合剂BAPTA-AM和钙蛋白酶2抑制剂钙肽素可显著抑制碲化镉量子点诱导的凋亡，并逆转这些蛋白的表达。本研究证实，暴露于碲化镉量子点会引发ND7/23细胞内质网应激，同时激活钙蛋白酶2-半胱天冬酶12信号通路，导致非线粒体依赖性凋亡。
