Publication: Caffeine Potentiates Ethanol-Induced Neurotoxicity Through mTOR/p70S6K/4E-BP1 Inhibition in SH-SY5Y Cells
Issued Date
2020-01-01
Resource Type
ISSN
1092874X
10915818
10915818
Other identifier(s)
2-s2.0-85078130183
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Toxicology. (2020)
Suggested Citation
Pongsak Sangaunchom, Permphan Dharmasaroja Caffeine Potentiates Ethanol-Induced Neurotoxicity Through mTOR/p70S6K/4E-BP1 Inhibition in SH-SY5Y Cells. International Journal of Toxicology. (2020). doi:10.1177/1091581819900150 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/53908
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Caffeine Potentiates Ethanol-Induced Neurotoxicity Through mTOR/p70S6K/4E-BP1 Inhibition in SH-SY5Y Cells
Author(s)
Other Contributor(s)
Abstract
© The Author(s) 2020. Caffeine is a popular psychostimulant, which is frequently consumed with ethanol. However, the effects of caffeine on neuronal cells constantly exposed to ethanol have not been investigated. Apoptosis and oxidative stress occurring in ethanol-induced neurotoxicity were previously associated with decreased phosphorylation of the mTOR/p70S6K/4E-BP1 signaling proteins. Evidence also suggested that caffeine inhibits the mTOR pathway. In this study, human SH-SY5Y neuroblastoma cells were exposed to caffeine after pretreatment for 24 hours with ethanol. Results indicated that both ethanol and caffeine caused neuronal cell death in a dose- and time-dependent manner. Exposure to 20-mM caffeine for 24 hours magnified reduced cell viability and enhanced apoptotic cell death induced by 200 mM of ethanol pretreatment. The phosphorylation of mTOR, p70S6K, and 4E-BP1 markedly decreased in cells exposed to caffeine after ethanol pretreatment, associated with a decrease of the mitochondrial membrane potential (ΔΨm). These findings suggested that caffeine treatment after neuronal cells were exposed to ethanol resulted in marked cell damages, mediated through enhanced inhibition of mTOR/p70S6K/4E-BP1 signaling leading to impaired ΔΨm and, eventually, apoptotic cell death.