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Sci. Signal., 2 March 2010
Vol. 3, Issue 111, p. ra15
[DOI: 10.1126/scisignal.2000502]
RESEARCH ARTICLES
Editor's Summary
Promoting Tolerance
A temporary or permanent interruption of blood flow (ischemia) to the brain can lead to brain injury, with potentially devastating consequences, such as stroke. Intriguingly, previous exposure to a brief period of ischemia that is not itself sufficient to cause brain injury can protect against a later, more prolonged period of ischemia. This phenomenon, called ischemic tolerance, is associated with a general suppression of gene expression in the tolerant brain. Paradoxically, the tolerant state depends on protein synthesis. Stapels et al. performed proteomic analyses of mouse brains subjected to various ischemic conditions and found, in ischemic-tolerant brains, an increase in the abundance of polycomb group proteins, which act as transcriptional repressors. Further analyses of both mouse brain and cultured cells indicated that the polycomb proteins SCMH1 and BMI1 inhibited potassium channel abundance and activity and that this represented a mechanism underlying ischemic tolerance. A further understanding of the mechanisms underlying tolerance could open the door to new therapies for ischemic stroke.
Citation: M. Stapels, C. Piper, T. Yang, M. Li, C. Stowell, Z.-g. Xiong, J. Saugstad, R. P. Simon, S. Geromanos, J. Langridge, J.-q. Lan, A. Zhou, Polycomb Group Proteins as Epigenetic Mediators of Neuroprotection in Ischemic Tolerance. Sci. Signal.3, ra15 (2010).
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