| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Outline of Final Research Achievements |
In this study, we analyzed the function of GADD34 on nutrition starvation-stress responses in macrophages. The deprivation of tyrosine and cysteine (Tyr/Cys) induced the expression of GADD34 in macrophages. LPS stimulation combined with Tyr/Cys-deprivation activated macrophages, then shifted to cell death in late phase of stimulation. A deficiency of GADD34 enhanced cell activation signaling and apoptosis more than that in wild-type macrophages. Further we found that mTOR-S6K signaling was higher in GADD34-deficient macrophages than in wild-type cells. Defective GADD34 reduced LC3-II and autophagosome formation induced by LPS-stimulation and Tyr/Cys-deprivation compared with that in wild-type macrophages. These results indicate that GADD34 enhances autophagy and suppresses apoptosis stimulated by LPS combined with amino acid deprivation through regulation of mTOR signaling pathway in macrophages.
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