Neuroprotective effects of 2-heptyl-3-hydroxy-4-quinolone in HT22 mouse hippocampal neuronal cells

Baskar Selvaraj; Dae Woon Kim; Jin-Soo Park; Hak Cheol Kwon; Heesu Lee; Ki-Yeon Yoo; Jae Wook Lee

doi:10.1016/j.bmcl.2021.128312

Neuroprotective effects of 2-heptyl-3-hydroxy-4-quinolone in HT22 mouse hippocampal neuronal cells

Bioorg Med Chem Lett. 2021 Oct 1:49:128312. doi: 10.1016/j.bmcl.2021.128312. Epub 2021 Aug 8.

Authors

Baskar Selvaraj¹, Dae Woon Kim², Jin-Soo Park³, Hak Cheol Kwon³, Heesu Lee⁴, Ki-Yeon Yoo⁴, Jae Wook Lee⁵

Affiliations

¹ Natural Product Research Center, Institute of Natural Product, Korea Institute of Science and Technology, Gangnueng 25451, Republic of Korea; Convergence Research Center of Dementia, Brain Science Institute, Korea Institute of Science and Technology, 02792, Republic of Korea; Division of Bio-medical Science & Technology, University of Science and Technology, Daejun 34113, Republic of Korea.
² Department of Biochemistry and Molecular Biology, Research Institute of Oral Science, College of Dentistry, Gangneung Wonju National University, 25457, Republic of Korea.
³ Natural Product Informatics Research Center, Institute of Natural Product, Korea Institute of Science and Technology, Gangnueng 25451, Republic of Korea.
⁴ Department of Oral Anatomy, College of Dentistry, Institute of Oral Science, Gangneung Wonju National University, Gangneung, Republic of Korea.
⁵ Natural Product Research Center, Institute of Natural Product, Korea Institute of Science and Technology, Gangnueng 25451, Republic of Korea; Convergence Research Center of Dementia, Brain Science Institute, Korea Institute of Science and Technology, 02792, Republic of Korea; Division of Bio-medical Science & Technology, University of Science and Technology, Daejun 34113, Republic of Korea. Electronic address: jwlee5@kist.re.kr.

PMID: 34375718
DOI: 10.1016/j.bmcl.2021.128312

Abstract

The neuroprotective activity of 2-heptyl-3-hydroxy-4(1H)-quinolone (compound 1) was evaluated using the neurotoxicity of glutamate in the HT22 cell line. Compound 1, known as a signal molecule of the bacterial quorum-sensing system, protects neuronal cells from glutamate-induced neurotoxicity by inhibiting cellular Ca²⁺ uptake and glutamate-triggered ROS accumulation. MAPK signaling pathway inhibition by compound 1 was evaluated by immunoblotting the phosphorylation status of the proteins. Furthermore, pro-apoptotic protein levels and AIF translocation to the nucleus were found to be reduced by compound 1. In conclusion, compound 1 showed neuroprotective effects by inhibiting apoptotic neuronal cell death.

Keywords: Glutamate; HT22 hippocampal neuronal cells; MAPK; Neuroprotective effects; Quinolone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis Inducing Factor / metabolism
Cell Line
Cell Survival / drug effects
Glutamic Acid / pharmacology
MAP Kinase Signaling System / drug effects
Mice
Neuroprotective Agents / pharmacology*
Oxidative Stress / drug effects
Proto-Oncogene Proteins c-bcl-2 / metabolism
Quinolones / pharmacology*
Reactive Oxygen Species / metabolism
bcl-2-Associated X Protein / metabolism

Substances

2-heptyl-3-hydroxy-4-quinolone
Apoptosis Inducing Factor
Bax protein, mouse
Neuroprotective Agents
AIFM1 protein, mouse
Proto-Oncogene Proteins c-bcl-2
Quinolones
Reactive Oxygen Species
bcl-2-Associated X Protein
Bcl2 protein, mouse
Glutamic Acid