Title page for etd-0504118-094049


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URN etd-0504118-094049
Author Chien-Jen Kao
Author's Email Address No Public.
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Department Marine Biotechnology and Resources
Year 2017
Semester 2
Degree Ph.D.
Type of Document
Language zh-TW.Big5 Chinese
Title The neuroprotective effects of modifying soft coral-derived compound
Date of Defense 2018-03-30
Page Count 101
Keyword
  • 1-tosylpentan-3-one
  • SH-SY5Y cells
  • zebrafish
  • 6-OHDA-induced apoptosis
  • marine compounds
  • neuroprotection
  • Abstract Previous studies have demonstrated that the marine compound austrasulfone, isolated from the soft coral Cladiella australis, exerts a neuroprotective effect. The intermediate product in the synthesis of austrasulfone, dihydroaustrasulfone alcohol, attenuates inflammatory responses. The present study uses in vitro and in vivo methods to investigate the neuroprotective effects of dihydroaustrasulfone alcohol-modified 1-tosylpentan-3-one (1T3O). Results from in vitro experiments show that 1T3O effectively inhibits 6-hydroxydopamine (6-OHDA)-induced activation of both p38 mitogen-activated protein kinase (MAPK) and caspase-3 in SH-SY5Y cells; and enhances nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling. Hoechst staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining results reveal that 1T3O significantly inhibits 6-OHDA-induced apoptosis. Moverover, the addition of an Akt or HO-1inhibitor decreases the protective effect of 1T3O. Thus, we hypothesize that the anti-apoptotic activity of 1T3O in neuronal cells is mediated through the regulation of the Akt and HO-1 signaling pathways. In vivo experiments show that 1T3O can reverse 6-OHDA-induced reduction in locomotor behavior ability in zebrafish larvae, and inhibit 6-OHDA-induced tumor necrosis factor-alpha (TNF-α) increase at the same time. According to our in vitro and in vivo results, we consider that 1T3O exerts its anti-apoptotic activities at SH-SY5Y cells after 6-OHDA challenges, probably via the regulation of anti-oxidative signaling pathways. Therefore, this compound may be a promising therapeutic agent for neurodegenerations.
    Advisory Committee
  • San-Nan Yang - chair
  • Wu, Chang-Yi - co-chair
  • Hui-Min David Wang - co-chair
  • Chien-Chih Chiu - co-chair
  • Wu-Fu Chen - co-chair
  • Wen Zhi-Hong - advisor
  • Files
  • etd-0504118-094049.pdf
  • Indicate in-campus at 99 year and off-campus access at 99 year.
    Date of Submission 2018-06-04

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