期刊
CELL DEATH AND DIFFERENTIATION
卷 20, 期 2, 页码 270-280出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2012.122
关键词
optic nerve injury; ASK1; p38; microglia; neural cell death
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Takeda Science Foundation
- Funding Program for Next Generation World-Leading Researchers (NEXT Program)
- Grants-in-Aid for Scientific Research [25462766, 25430082, 23659033, 23792024, 24791884, 20229004, 22591929, 23890254] Funding Source: KAKEN
Optic nerve injury (ONI) induces retinal ganglion cell (RGC) death and optic nerve atrophy that lead to visual loss. Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced RGC apoptosis. In this study, we found that ONI-induced p38 activation and RGC loss were suppressed in ASK1-deficient mice. Sequential in vivo retinal imaging revealed that post-ONI treatment with a p38 inhibitor into the eyeball was effective for RGC protection. ONI-induced monocyte chemotactic protein-1 production in RGCs and microglial accumulation around RGCs were suppressed in ASK1-deficient mice. In addition, the productions of tumor necrosis factor and inducible nitric oxide synthase in microglia were decreased when the ASK1-p38 pathway was blocked. These results suggest that ASK1 activation in both neural and glial cells is involved in neural cell death, and that pharmacological interruption of ASK1-p38 pathways could be beneficial in the treatment of ONI. Cell Death and Differentiation (2013) 20, 270-280; doi:10.1038/cdd.2012.122; published online 14 September 2012
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