Year: 2026
Type: article
Abstract: Ergothioneine (ERGO) is a naturally occurring thiol-containing amino acid derived from histidine and obtained exclusively through dietary intake, particularly from mushrooms. ERGO has been identified as a potent antioxidant and cytoprotective molecule that accumulates in mammalian tissues via the organic cation transporter OCTN1 (SLC22A4). In this study, we investigated two major biological effects of ERGO using rat adrenal pheochromocytoma PC12 cells: (1) its protective effect against hydrogen peroxide (H₂O₂)-induced oxidative stress and (2) its regulatory effect on neuronal differentiation induced by nerve growth factor (NGF). Cell viability and cytotoxicity were assessed by MTT and LDH assays, respectively. Western blot analysis revealed that ERGO suppressed oxidative stress-induced phosphorylation of MAPKs, including p38 and JNK. Furthermore, ERGO enhanced NGF-induced neurite outgrowth in a dose-dependent manner. These findings suggest that ERGO functions not only as an antioxidant but also as a modulator of neuronal differentiation signaling, potentially via MAPK and mTOR–S6K pathways. Cell proliferation was evaluated using the MTT assay. As expected, oxidative stress induced by H₂O₂ inhibited cellular growth. However, when H₂O₂ was administered alongside ERGO, this growth inhibition was alleviated. This observation suggests that ERGO promotes cellular proliferation in the presence of H₂O₂, and that is likely due to its antioxidant properties. The effect of ERGO on the MAPK pathway activated by oxidative stress H₂O₂ increased the activity of stress-related proteins, p38 and JNK. In contrast, the addition of ERGO reduced the activity of these proteins. This indicates that ERGO decreases reactive oxygen species and inhibits the activity of stress-related proteins. The effect of ERGO on NGF-induced neuronal differentiation NGF induced the differentiation of PC-12 cells into neuron-like structures, characterized by elongated extensions. The addition of ERGO further promoted the growth of these extensions in a dose-dependent manner. This implies that ERGO facilitates neuronal growth by augmenting NGF signaling.
Author: Tsuchiya, Yoshihiro
Language: Japanese
Topic: Sulfur Compounds in Biology
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7208579751