Protective autophagy alleviates neurotoxin-gelsenicine induced apoptosis through PERK signaling pathway in Neuro-2a cells

In this study, Neuro-2a cells were used to be our object of study for determining the mechanism by which gelsenicine induced neurotoxicity. We found that gelsenicine is neurotoxic to Neuro-2a cells; indeed cell proliferation was inhibited and apoptosis was induced in a dose-dependent manner. Meanwhile, gelsenicine markedly promoted autophagy and activated autophagic flux. Additionally, promoting autophagy with rapamycin decreased apoptosis, whereas blocking autophagy with 3-methyladenine (3-MA) increased apoptosis. Furthermore, the protein kinase ribose nucleic acid (RNA)-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α)/activating transcription factor 4 (ATF4) signaling pathway was involved in the induction of protective autophagy in Neuro-2a cells. Inhibition of PERK using small interfering RNA (siRNA) inhibited gelsenicine-induced autophagy and aggravated apoptosis. These data indicate that gelsenicine not only exhibited cytotoxicity and induced apoptosis, but it also induced protective autophagy via PERK signaling pathway to alleviate gelsenicine-mediated apoptosis in Neuro-2a cells.PMID:35588915 | DOI:10.1016/j.tox.2022.153210
Source: Toxicology - Category: Toxicology Authors: Source Type: research