July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Key pathways and genes influenced by a drug, NK-4, in human neurons
Author Affiliations & Notes
  • Shihui Liu
    Ophthalmology, Okayama University, Okayama, Japan
  • Toshihiko Matsuo
    Ophthalmology, Okayama University, Okayama, Japan
  • Mary Miyaji
    Medical Neurobiology, Okayama University, Okayama, Japan
  • Osamu Hosoya
    Medical Neurobiology, Okayama University, Okayama, Japan
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6051. doi:
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      Shihui Liu, Toshihiko Matsuo, Mary Miyaji, Osamu Hosoya; Key pathways and genes influenced by a drug, NK-4, in human neurons. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6051.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : NK-4 (4,4’-[3-{2-(1-ethyl-4(1H)-quinolylidene)ethylidene}pro-penylene]bis(1- ethylquinolinium iodide)) (lumin) has a variety of biological activities, such as antimicrobial, macrophage-activating, anticancer properties, and has a potential role in suppressing the apoptosis of photoreceptor in an animal model of retinitis pigments, Royal College of Surgeons (RCS) rats (Liu S, et al. Invest. Ophthalmol. Vis. Sci.. 2017; 58(8):277. doi:). The aim of this study was to investigate gene signatures about anti-apoptotic mechanism exerted by lumin, and to uncover their potential mechanisms in human neurons.

Methods : Human neural cells (SCR:1520-5) were cultured and the whole RNA was extracted. The library was prepared by a kit (TruSeq RNA Sample Prep Kit v2), and transcriptome sequencing was performed on the platform of HiSeq2500 (Illumina). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were conducted, and protein–protein interaction (PPI) network of differentially expressed genes (DEGs) was created by Metascape software.

Results : In total, 564 DEGs were identified in the presence of lumin, including 281 up-regulated genes and 283 down-regulated genes. Pathway enrichment analysis by Metascape showed that up-regulated DEGs were significantly enriched in GO biological processes and KEGG pathways, including apoptotic signaling pathway, negative regulation of apoptotic signaling pathway, positive regulation of cell death, and PI3K-Akt signaling pathway. PPI net-work analysis revealed these genes were involved in significant pathways, including hallmark MTORC1 signaling, hallmark unfolded protein response, hallmark TNFA signaling via NFKB. The down-regulated DEGs were significantly enriched in GO biological processes, including chemical synaptic transmission, synapse organization, and regulation of nervous system development.

Conclusions : The identified DEGs and hub genes would give a key for understanding molecular mechanisms underlying the role of lumin in apoptotic suppression, and might be used as molecular targets and diagnostic biomarkers for the treatment of neuronal apoptosis in human. Additional experiments that investigate the mechanisms for inhibiting apoptosis of neurons with NK-4 are in progress.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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