Parkinsonism-Associated Protein DJ-1 Is an Antagonist, Not an Eraser, for Protein Glycation.
Parkinsonism-Associated Protein DJ-1 Is an Antagonist, Not an Eraser, for Protein Glycation.
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DOI：
10.1021/acs.biochem.3c00028
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发表时间：
2023-03-21
期刊：
影响因子：
2.9
通讯作者：
Scheck, Rebecca A.
中科院分区：
文献类型：
--
作者：
Gao, Qingzeng;Jacob-Dolan, Jeremiah W.;Scheck, Rebecca A.
晚期糖基化终产物（AGEs）是一种不可逆的蛋白质修饰，与衰老和疾病密切相关。最近，帕金森病相关蛋白DJ-1已被报道表现出去糖酶活性，从蛋白质中清除早期糖基化中间体和稳定的AGEs。在这项工作中，我们使用质谱和蛋白质印迹证明DJ-1不是一个degylase，不能从蛋白质或肽底物中去除AGEs。相反，我们的研究表明，DJ-1拮抗糖化通过谷胱甘肽酶活性，解毒的有效糖化剂甲基乙二醛（MGO）乳酸。我们进一步表明，在DJ-1的存在下，减弱的糖基化可以仅仅归因于其降低MGO的可用浓度的能力。我们的研究还提供了证据，DJ-1是由谷胱甘肽变构激活。总之，这项工作表明，虽然DJ-1不是一个真正的deglycase，但它仍然具有阻止AGE形成的能力，可以作为研究代谢应激的有价值的工具。
Advanced glycation end-products (AGEs) are irreversible protein modifications that are strongly associated with aging and disease. Recently, the Parkinsonism-associated protein DJ-1 has been reported to exhibit deglycase activity that erases early glycation intermediates and stable AGEs from proteins. In this work, we use mass spectrometry and western blot to demonstrate that DJ-1 is not a deglycase and cannot remove AGEs from protein or peptide substrates. Instead, our studies revealed that DJ-1 antagonizes glycation through glyoxalase activity that detoxifies the potent glycating agent methylglyoxal (MGO) to lactate. We further show that attenuated glycation in the presence of DJ-1 can be attributed solely to its ability to decrease the available concentration of MGO. Our studies also provide evidence that DJ-1 is allosterically activated by glutathione. Together, this work reveals that although DJ-1 is not a genuine deglycase, it still harbors the ability to prevent AGE formation and can be used as a valuable tool to investigate metabolic stress.
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