Journal article
Neuronal necrosis is regulated by a conserved chromatin-modifying cascade
Proceedings of the National Academy of Sciences - PNAS, Vol.111(38), pp.13960-13965
09/23/2014
DOI: 10.1073/pnas.1413644111
PMCID: PMC4183342
PMID: 25201987
Abstract
Neuronal necrosis induced by calcium overload causes devastating brain dysfunction in diseases such as stroke and brain trauma. It has been considered a stochastic event lacking genetic regulation, and pharmacological means to suppress neuronal necrosis are lacking. Using a Drosophila model of calcium overloading, we found JIL-1/mitogen- and stress-activated protein kinase 1/2 is a regulator of neuronal necrosis through phosphorylation of histone H3 serine 28 (H3S28ph). Further, we identified its downstream events including displacement of polycomb repressive complex 1 (PRC1) and activation of Trithorax (Trx). To test the role of JIL-1/PRC1/Trx cascade in mammals, we studied the necrosis induced by glutamate in rat cortical neuron cultures and rodent models of brain ischemia and found the cascade is activated in these conditions and inhibition of the cascade suppresses necrosis in vitro and in vivo. Together, our research demonstrates that neuronal necrosis is regulated by a chromatin-modifying cascade, and this discovery may provide potential therapeutic targets and biomarkers for neuronal necrosis.
Details
- Title: Subtitle
- Neuronal necrosis is regulated by a conserved chromatin-modifying cascade
- Creators
- Kai Liu - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, ChinaLianggong Ding - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, ChinaYuhong Li - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, China; Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242Hui Yang - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, ChinaChunyue Zhao - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, ChinaYe Lei - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, ChinaShuting Han - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, ChinaWei Tao - The Education Ministry Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, ChinaDengshun Miao - State Key Laboratory of Reproductive Medicine, Research Center for Bone and Stem Cells, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu 210029 ChinaHermann Steller - Howard Hughes Medical Institute, Strang Laboratory of Apoptosis and Cancer Biology, The Rockefeller University, New York, NY 10065; andMichael J Welsh - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242; michael-welsh@uiowa.edu leiliu@pku.edu.cnLei Liu - The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Peking University, Beijing 100871, China; Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Youanmen, Beijing 100069, China michael-welsh@uiowa.edu leiliu@pku.edu.cn
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.111(38), pp.13960-13965
- DOI
- 10.1073/pnas.1413644111
- PMID
- 25201987
- PMCID
- PMC4183342
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences; United States
- Grant note
- R01 GM060124 / NIGMS NIH HHS P30 ES005605 / NIEHS NIH HHS Howard Hughes Medical Institute
- Language
- English
- Date published
- 09/23/2014
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020622402771
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