The role of tau protein in the pathogenesis of salivary gland of SS patients

• Project/Area Number: 26670819
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Nagasaki University
• Principal Investigator: NAKAMURA Takashi 長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30172406)
• Co-Investigator(Kenkyū-buntansha): HOTOKEZAKA Yuka 長崎大学, 病院(歯学系), 講師 (10244089) ; KATAYAMA Ikuo 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (80295089)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: cPLA2 / 細胞死 / シェーグレン / tau

Outline of Final Research Achievements

We analyzed the cell death mechanisms of different cell death types to understand the multiplicity of their mechanisms. We have found that double strand break DNA damage transmits cell death signals via the AKT/GSK3β/αNAC/γtaxilin pathway that is used when the cell death in hypoxic stress. Our hypothesis is that cPLA2 can exert its action on the ER membrane rather than the plasma membrane in the case of several cell stresses including DNA damage and hypoxia. Hypoxic stress is a candidate for the pathogenesis of degenerative changes in the salivary gland of patients with Sjogren’s syndrome (SS) as is generally considered in the pathogenesis of brain degenerative disorders such as Alzheimer’s disease. In fact, we found that lung fibroblasts (MLF) established from cPLA2-/- mice are resistant against hypoxic and DNA damage stresses. Therefore, we speculate that cPLA2 a causative factor that involved in the pathogenesis of salivary g;land disorders in SS patients.

Research Products

• [Journal Article] Length of intact plasma membrane determines the diffusion properties of cellular water (2016)
  • Author(s): Sato Eida, Marc Van Cauteren, Yuka Hotokezaka, Ikuo Katayama, Miho Sasaki, Makoto Obara, Tomoyuki Okuaki, Misa Sumi, Takashi Nakamura
  • Journal Title: Scientific Reports Volume: 6 ;19051 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep19051
  • NAID: 120006987227
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GSK3β-dependent downregulation of γ-taxilin and αNAC merge to regulate ER stress responses. (2015)
  • Author(s): Hotokezaka Y, Katayama I, van Leyen K, Nakamura T
  • Journal Title: Cell Death Dis Volume: 6
  • NAID: 120006987615
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant