| Project/Area Number |
22390248
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Takuro 福島県立医科大学, 医学部, 医監兼教授 (20305361)
ANAZAWA Takayuki 福島県立医科大学, 医学部, 助教 (90566811)
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| Co-Investigator(Renkei-kenkyūsha) |
KENJO Akira 福島県立医科大学, 医学部, 講師 (40305355)
ISE Kazuya 福島県立医科大学, 医学部, 講師 (90363746)
KIMURA Takashi 福島県立医科大学, 医学部, 助教 (00381369)
SUZUKI Hiroyuki 福島県立医科大学, 医学部, 教授 (30322340)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2010: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 膵島 / 亜致死刺激 / 免疫寛容 / 細胞周期停止 / Mitomycin C / HMGB1 / calreticulin / 細胞死 / 移植 / 酸化ストレス / 小胞体ストレス |
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| Research Abstract |
Islets treated with sublethal concentration of MMC at 10μg/ml for 30 min induced immunological unresponsiveness when these islets were cultured for more than 20 hrs and transplanted into renal subcapsular space of STZ-induced diabetic mice. MMC treatment effectively reduced central necrotic area which pooled calreticulin and HMGB1 both inducing cross priming together. Western blot analysis suggested that MMC treatment and subsequent culture for 8 or 20 h upregulated the active form of p53 as well as the downstream gene p21waf1. Meanwhile, the active form of caspase-3 was not significantly changed. This indicates that the activation of p53 was directed at cell cycle arrest, but not at apoptosis processes through the activation of caspase-3. These findings together with previous in vivo results would support that a concept of surviving but not dying cells through sublethal stress induce unresponsiveness to the treated cells.
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