TIAN Xin-li, SHANGGUAN Jun-fa, CHEN Li-ping, LI Xiao-gang
Current Immunology. 2025, 45(2): 164.
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The aim of this study was to investigate the effect of engeletin (Eng) on the autophagy of neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) by the PTEN-induced kinase 1 (PINK1)/Parkin signaling pathway. The mouse hippocampal neuron HT22 cell line was used as the study object to establish an OGD/R-induced cell damaged model. HT22 cells were grouped into the model group (OGD/R group), the low-, medium- and high-dose Eng groups (Eng-L, -M, -H groups, with 1, 5, 10 mmol/L Eng, respectively), the si-PINK1 NC+Eng-H group, the si-PINK1+Eng-H group, and blank group (control group). The cell viability, cell apoptosis, reactive oxygen species (ROS) level, the cell levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD),the changes of mitochondrial membrane potential, cell autophagy level, the expressions of PINK1, Parkin (E3 ubiquitin ligase), microtubule-associated protein 1 light chain 3 (LC3), ubiquitin-binding protein p62, and caspase3 were evaluated using appropriate methods. The results showed that compared to those of the control group, the viability of HT22 cells, the GSH-Px, the SOD levels, the mitochondrial membrane potential, the cell autophagy level, the ratio of LC3-Ⅱ/LC3-Ⅰ, and the protein expressions of PINK1 and Parkin in the OGD/R group were significantly decreased (all with P<0.05), whereas the apoptosis rate, the caspase3 protein expression, ROS, MDA levels, and p62 protein expression all significantly increased (all with P<0.05). Compared to those of the OGD/R group, the viability of HT22 cells, the GSH-Px, SOD levels, the mitochondrial membrane potential, the cell autophagy level, the ratio of LC3-Ⅱ/LC3-Ⅰ, and the protein expressions of PINK1 and Parkin in the Eng-L、-M and -H groups were significantly increased (all with P<0.05) while the apoptosis rate, the caspase3 protein expression, ROS, MDA levels and the p62 protein expression all significantly decreased (all with P<0.05). Compared to the Eng-H group, si-PINK1+Eng-H treatment reversed the effect of Eng-H on the enhancement of autophagy of HT22 cells, and aggravated cell injury and apoptosis. In conclusion, we have firstly demonstrated that Eng can up-regulate the expression of PINK1/Parkin signaling pathway, and alleviate OGD/R-induced neuronal damage through the mitochondrial autophagy pathway.