Transient elevation of temperature promotes cross-linking of α-crystallin-client proteins through formation of advanced glycation endproducts: A potential role in presbyopia and cataracts.
Transient elevation of temperature promotes cross-linking of α-crystallin-client proteins through formation of advanced glycation endproducts: A potential role in presbyopia and cataracts.
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温度的瞬时升高可通过形成晚期糖基化最终产物来促进α-晶蛋白 - 晶状体蛋白的交联：在长叶和白内障中的潜在作用。
DOI：
10.1016/j.bbrc.2020.10.018
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Nagaraj RH
中科院分区：
文献类型：
--
作者：
Nandi SK;Rankenberg J;Glomb MA;Nagaraj RH
α-晶状体蛋白的分子伴侣活性对于维持人透镜的透明度是重要的。α B-晶状体蛋白（αBC）是透镜中的一种长寿命蛋白质，其在老化过程中积累化学修饰。通过糖基化形成晚期糖基化终产物（AGEs）就是这样一种修饰。αBC是一种小的热休克蛋白，具有分子伴侣活性。我们先前已经证明，α BC-客户蛋白复合物可以进行AGE介导的蛋白质间交联。在这里，我们证明，短期（1小时）暴露于高温和甲基乙二醛（MGO）在客户蛋白的伴侣通过αBC促进AGE介导的蛋白质间交联。液相色谱/质谱（LC-MS/MS）分析表明，AGEs的快速形成的MGO。有趣的是，我们发现，尽管蛋白质交联，但在MGO存在下，αBC的伴侣活性在温度瞬时升高期间增加。总之，这些结果意味着眼睛透镜中短暂和微妙的温度升高可以通过AGEs促进蛋白质交联，如果这种现象在多年的时间内复发，它可能导致老花眼和年龄相关性白内障的早期发作。
The chaperone activity of α-crystallin is important for maintaining the transparency of the human lens. αB-crystallin (αBC) is a long-lived protein in the lens that accumulates chemical modifications during aging. The formation of advanced glycation end products (AGEs) through glycation is one such modification. αBC is a small heat shock protein that exhibits chaperone activity. We have previously shown that αBC-client protein complexes can undergo AGE-mediated interprotein cross-linking. Here, we demonstrate that short-term (1 h) exposure to elevated temperatures and methylglyoxal (MGO) during the chaperoning of client proteins by αBC promotes AGE-mediated interprotein cross-linking. Liquid chromatography/mass spectrometry (LC-MS/MS) analyses revealed the rapid formation of AGEs by MGO. Interestingly, we found that despite protein cross-linking, the chaperone activity of αBC increased during the transient elevation of temperature in the presence of MGO. Together, these results imply that transient and subtle elevation of temperature in the lens of the eye can promote protein cross-linking through AGEs, and if this phenomenon recurs over a period of many years, it could lead to early onset of presbyopia and age-related cataracts.
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影响因子：
1.9
作者：
KRAMAR, P;HARRIS, C;GUY, AW
通讯作者：
GUY, AW
影响因子：
5.8
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PHILLIPS, SA;MIRRLEES, D;THORNALLEY, PJ
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THORNALLEY, PJ
影响因子：
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Rakete, Stefan;Nagaraj, Ram H.
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Nagaraj, Ram H.
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通讯作者：
Das, KP
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2.9
作者：
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通讯作者：
Nagaraj, Ram H.