Title page for etd-0715118-011503


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URN etd-0715118-011503
Author Yu-Chin Huang
Author's Email Address No Public.
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Department Institute of Biomedical Sciences
Year 2017
Semester 2
Degree Master
Type of Document
Language English
Title Role of FNDC5/Irisin in neurogenesis of SH-SY5Y cells
Date of Defense 2018-07-13
Page Count 71
Keyword
  • neuroprotection
  • Irisin
  • exercise
  • neuronal differentiation
  • Abstract People who live in high-pressure work environment and lacking enough exercise of lifestyle frequently elicit several metabolic syndromes or cardiovascular diseases.  Studies have shown that exercise not only enhance immune system and reduce the incidence of civil diseases, but also help patients with neurological disorders to regain lost physical abilities. However, how beneficial effects of exercise on neuroprotection or neuronal differentiation is still unclear. Irisin, a newly myokine protein, which has been shown to be secreted from transmembrane protein fibronectin type III domain containing 5 (FNDC5) of skeletal muscle. Studies have indicated that Irisin is efficient to induce converting differentiation of white adipose tissue into brown adipose tissue and improve type 2 diabetes. Moreover, Irisin is also shed as a potential regulator in neuronal survival and development. Thus, in this study, we investigated the role of IrisinWT and Irisin-mutnat recombinant proteins in neuronal differentiation and neuron protection. According to the crystal structure and biochemical results supported that IrisinWT can form a dimerization by salt bridge region and disulfide bond, we thus generated IrisinWT and point mutation of IrisinR75E, IrisinC87A and IrisinR75EC87A proteins to address this aim. By proliferation and migration assays, our results indicated that IrisinWT stimulate the cell proliferation and migration in SH-SY5Y cells in dose manner. In addition, IrisinWT reduced the cell death induced by 6-OHDA or CoCl2 in SH-SY5Y cells. Moreover, RT-PCR and Western blot results revealed that an elevation of mRNA and protein level of IrisinWT in Retinoic acid (RA)-induced neuron-like cells. In summary, our results suggested that IrisinWT protect neuron cells against neurotoxin 6-OHDA-induced cell damage and protect neuron cells against CoCl2-induced cell damage in a hypoxic environment. On the other hand, Irisin-mutant proteins were only partially or unable to protect neuronal cells from neurotoxin 6-OHDA-induced cell injury and protect neuronal cells from CoCl2-induced cell damage in a hypoxic environment. Taken together, the results implied that the dimerization of Irisin is important for its bio-function, and the formation of disulfide bonds is critical to the dimerization of Irisin.
    Advisory Committee
  • Jinn-Chyuan Sheu - chair
  • Zhi-Hong Wen - co-chair
  • Ming-Hong Tai - advisor
  • Files
  • etd-0715118-011503.pdf
  • Indicate in-campus at 99 year and off-campus access at 99 year.
    Date of Submission 2018-08-15

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