Retinal proteomic changes under different ischemic conditions - implication of an epigenetic regulatory mechanism.
Retinal proteomic changes under different ischemic conditions - implication of an epigenetic regulatory mechanism.
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发表时间：
2010-06
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通讯作者：
C. Stowell;Lin Wang;B. Arbogast;J. Lan;G. Cioffi;C. Burgoyne;A. Zhou
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作者：
C. Stowell;Lin Wang;B. Arbogast;J. Lan;G. Cioffi;C. Burgoyne;A. Zhou
在视网膜中，亚致死性缺血治疗（预处理）可在其他损伤性缺血损伤之前诱导缺血性损伤抵抗状态（缺血耐受）。在这项工作中，我们比较了三种不同的缺血条件下视网膜蛋白质组学的变化，作为一种手段来确定视网膜缺血耐受的效应机制。通过升高眼内压（IOP）诱导三组成年大鼠短暂性视网膜缺血：第1组，缺血预处理，110 mmHg 8 min，再灌注48 h；2组，缺血损伤，110 mmHg 60分钟，24小时再灌注；3组，耐受缺血，预处理后再灌注60分钟110 mmHg， 24小时再灌注。通过定量质谱测定的上述每种视网膜缺血条件下的蛋白质量与对侧对照眼（假治疗）的蛋白质量进行比较。结果，共鉴定和定量了328个蛋白；其中，30-60%的蛋白质在一种或多种视网膜缺血条件下丰度发生变化。特别是在缺血耐受视网膜中，组蛋白H2B、H3和H4丰度增加，而组蛋白H2A丰度减少。进一步的免疫组织化学分析证实了蛋白质组学分析的结果，检测到三甲基化组蛋白H3、单泛素化组蛋白H2A和Polycomb组蛋白RING2的上调。总之，这些结果表明表观遗传调控在诱导视网膜缺血耐受性中的作用涉及组蛋白和多梳蛋白。
In retina, an ischemic injury-resistant condition (ischemic tolerance) can be induced by a sub-lethal ischemic treatment (preconditioning) prior to an otherwise injurious ischemic insult. In this work, we compared retinal proteomic changes under three different ischemic conditions, as a means to identify the effector mechanisms that underlie retinal ischemic tolerance. Transient retinal ischemia was induced by elevating the intraocular pressure (IOP) in three groups of adult rats as follows: Group 1, ischemic-preconditioned, 110 mmHg for 8 minutes followed by 48 hours reperfusion; Group 2, ischemic-injured, 110 mmHg for 60 minutes followed by 24 hours reperfusion; Group 3, ischemic-tolerant, preconditioning treatment followed by another 60 minutes of 110 mmHg and 24 hours reperfusion. Protein quantities in each of the afore-mentioned retinal ischemic conditions, as determined by quantitative mass spectrometry, were compared with that of the contralateral control eyes (sham-treated). As a result, a total of 328 proteins were identified and quantified; among them, 30-60% of proteins showed a change in abundance under one or more retinal ischemic conditions. In particular, in ischemic-tolerant retinas, histone proteins H2B, H3 and H4 demonstrated an increase in abundance, whereas histone H2A showed a decrease in abundance. Further immunohistochemical analyses confirmed the results of proteomic analyses, and detected an up regulation of tri-methylated histone H3, mono-ubiquitinated histone H2A and Polycomb group protein RING2. Together, these results suggest a role of epigenetic regulation in the induction of retinal ischemic tolerance that involves histone and polycomb proteins.