Geranylgeranyl Acetone Prevents Glutamate-induced Cell Death in HT-22 Cells by Increasing Mitochondrial Membrane Potential

Abstract

Geranylgeranyl acetone (GGA) protects against various types of cell damages by upregulating heat shock proteins. We investigated whether GGA protect neuronal cells from cell death induced by oxidative stress. Glutamate exposure was lethal to HT-22 cells which comprise a neuronal line derived from mouse hippocampus. This configuration is often used as a model for hippocampus neurodegeneration in vitro. In the present study, GGA protected HT-22 cells from glutamate-induced oxidative stress. GGA pretreatment did not induce Hsps. Moreover, reactive oxygen species increased to the same extent in both GGA-pretreated and untreated cells exposed to glutamate. In contrast, glutamate exposure and GGA pretreatment increased mitochondrial membrane potential. However, increases in intracellular Ca2+ concentration were inhibited by GGA pretreatment. In addition, the increase of phosphorylated ERKs by the glutamate exposure was inhibited by GGA pretreatment. These findings suggest that GGA protects HT-22 cells from glutamate-provoked cell death without Hsp induction and that the mitochondrial calcium buffering capacity plays an important role in this protective effect.

Screening of the active Ingredients in Huanglian Jiedu decoction through amide bond-Immobilized magnetic nanoparticle-assisted cell membrane chromatography

“…Because hippocampal neuronal HT-22 cells do not express iGluR, their glutamate-induced excitotoxicity is negligible (Sato et al, 2016;Phung, et al, 2020). Therefore, glutamate-treated HT-22 cells are widely used as ideal models for model for oxidative stress injury (Bonaterra et al, 2017;Sugano et al, 2020). In the present study, a glutamate-induced cell damage model was used to evaluate specific binding components.…”

Lung–brain axis: Metabolomics and pathological changes in lungs and brain of respiratory syncytial virus‐infected mice

“…Another protective mechanism is geranylgeranyl acetone (GGA). GGA protects HT‐22 cells from glutamate‐provoked cell death without HSP induction 19 . In a bid to establish the biological pathways involving lung brain axis using RSV mouse model, we designed this methodological approach.…”

“…GGA protects HT-22 cells from glutamate-provoked cell death without HSP induction. 19 In a bid to establish the biological pathways involving lung brain axis using RSV mouse model, we designed this methodological approach. To identify novel treatment based on the use of physiological protective metabolites, this study aimed to investigate the role of metabolites in the RSVassociated neurologic syndromes as well as to further dissect the molecular mechanisms at the basis of RSV-induced long-term nerve disorders.…”