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血红蛋白的赖氨酸乳酰化促进红细胞中的氧气释放。

Lysine Lactylation of Hemoglobin Promotes Oxygen Release in Red Blood Cells.

作者信息

Sheng Ming, Jin Huiqin, Tao Shiyu, You Guoxing, Li Weidan, Chang Chen, Wang Ying, Zhao Lian, Zhou Hong

机构信息

Academy of Military Medical Sciences, Academy of Military Science of the Chinese People's Liberation Army, No. 27 Taiping Road, Haidian, 100850 Beijing, P.R. China.

出版信息

ACS Omega. 2025 May 19;10(21):21889-21907. doi: 10.1021/acsomega.5c01888. eCollection 2025 Jun 3.

DOI:10.1021/acsomega.5c01888
PMID:40488064
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12138696/
Abstract

Hemoglobin oxygen affinity (HOA) increases during the storage of red blood cells (RBCs), which hinders the oxygen-release efficacy after transfusion. RBCs stored in alkaline preservation solution promote glycolysis and its final product lactate, which is an allosteric regulator of HOA. In recent years, lactylation has been widely studied, and the degree of lactylation is positively associated with the lactate concentration. However, it is unclear whether lactate can participate in the allosteric regulation of HOA via lactylation when lactate accumulates to a certain level during RBC storage in alkaline preservation solutions. Therefore, we prepared preservation solutions with the same formulation but different pH values and investigated the changes in P, which represent HOA, and lactate levels. We also performed comprehensive analysis on the lactylation of stored RBCs via molecular dynamics simulation and confirmed the effects of lactylation on hemoglobin (Hb) via in vitro experiments. We found lactylation modifications in RBCs and less storage damage when stored in alkaline preservation solutions. Lactylation acts predominantly on the lysine 66 site of the Hb β-subunit. Lactylation promotes conformational changes of Hb from the relaxed (R) state to the tight (T) state, which in turn promotes oxygen release from RBCs.

摘要

红细胞（RBC）储存期间血红蛋白氧亲和力（HOA）增加，这会阻碍输血后的氧释放效果。储存在碱性保存液中的红细胞会促进糖酵解及其终产物乳酸的生成，乳酸是HOA的变构调节因子。近年来，乳酸化受到广泛研究，乳酸化程度与乳酸浓度呈正相关。然而，在碱性保存液中红细胞储存期间，当乳酸积累到一定水平时，乳酸是否能通过乳酸化参与HOA的变构调节尚不清楚。因此，我们制备了配方相同但pH值不同的保存液，并研究了代表HOA的P值和乳酸水平的变化。我们还通过分子动力学模拟对储存红细胞的乳酸化进行了综合分析，并通过体外实验证实了乳酸化对血红蛋白（Hb）的影响。我们发现红细胞存在乳酸化修饰，且储存在碱性保存液中时储存损伤较小。乳酸化主要作用于Hbβ亚基的赖氨酸66位点。乳酸化促进Hb从松弛（R）状态向紧密（T）状态的构象变化，进而促进红细胞释放氧气。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/1f8d82e68c35/ao5c01888_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/144e2d21b383/ao5c01888_0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/c08c3f7ed922/ao5c01888_0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/1f8d82e68c35/ao5c01888_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/144e2d21b383/ao5c01888_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/bf063da12dd4/ao5c01888_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/821b92c8a08e/ao5c01888_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/d27c15c62416/ao5c01888_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/e58d7031804b/ao5c01888_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/c08c3f7ed922/ao5c01888_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/b45bff821b31/ao5c01888_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9492/12138696/1f8d82e68c35/ao5c01888_0008.jpg

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本文引用的文献

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NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance.高效的DNA修复和化疗耐药性需要NBS1乳酸化。
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Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation.星形胶质细胞 LRP1 通过抑制 ARF1 的乳酰化来实现线粒体向神经元的转移，并减轻脑缺血性中风。
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