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SIP30 (ZWINT1), a placental mammal specific gene, modulates stimulated vesicle exocytosis and neuropathic pain

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2009, PhD, University of Cincinnati, Medicine : Cell and Molecular Biology.
SIP30 is a multifunctional protein that participates in different molecular and cellular processes through its interaction with various molecular partners. In an effort to identify molecular regulators for neuropathic pain, the mRNA of SIP30 was discovered to be up-regulated in the side of spinal cord ipsilateral to peripheral nerve damage in rats receiving chronic constriction injury (CCI) of sciatic nerve surgery. When CCI induced up-regulation of SIP30 was inhibited by intrathecal administration of antisense oligonucleotide, neuropathic pain was attenuated, suggesting a cause-effect relationship between SIP30 up-regulation and neuropathic pain. We also showed that SIP30 gene was evolutionarily restricted to placental mammals, paralleling the phylogenetic occurrence of neuropathic pain. The interactions between SIP30 and SNAP25, SIP30 and Rab3 suggested a potential involvement of SIP30 in stimulated vesicle exocytosis. Using a human growth hormone (hGH) secretion assay in PC12 cells, anti-SIP30 siRNA transfection reduced the exocytosis of transfected hGH, which indicated that the exocytosis was attenuated. Electron microscopy imaging analysis revealed that the reduction in releasable vesicles was not due to reduced vesicle biogenesis. Study of vesicle exocytosis from PC12 cells with FM1-43 demonstrated that SIP30 siRNA reduced the pool of releasable vesicles and the rate of vesicle exocytosis. When the expression of SIP30 was inhibited, a reduction in the expression of SNAP25 was also observed both in CCI rats and in PC12 cells, which suggested a close functional relevance between SIP30 and SNAP25. In conclusion, SIP30 participates in vesicle exocytosis and its up-regulation in spinal cord caused by nerve injury is necessary for neuropathic pain.
Lei Yu, PhD (Committee Chair)
Anil Menon, PhD (Committee Member)
James Herman, PhD (Committee Member)
Robert Brackenbury, PhD (Committee Member)
Linda Parysek, PhD (Committee Member)
162 p.

Recommended Citations

Citations

  • Guo, N. (2009). SIP30 (ZWINT1), a placental mammal specific gene, modulates stimulated vesicle exocytosis and neuropathic pain [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1236015122

    APA Style (7th edition)

  • Guo, Ning. SIP30 (ZWINT1), a placental mammal specific gene, modulates stimulated vesicle exocytosis and neuropathic pain. 2009. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1236015122.

    MLA Style (8th edition)

  • Guo, Ning. "SIP30 (ZWINT1), a placental mammal specific gene, modulates stimulated vesicle exocytosis and neuropathic pain." Doctoral dissertation, University of Cincinnati, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1236015122

    Chicago Manual of Style (17th edition)