乳酰化修饰在疾病中的作用及机制研究进展

doi:10.3969/j.issn.1674-8115.2023.03.014

摘要/Abstract

摘要：

乳酸是细胞呼吸的产物。葡萄糖进入细胞后，在己糖激酶等的催化作用下通过糖酵解代谢成丙酮酸。当细胞氧供充足时，丙酮酸通过线粒体基质中的丙酮酸脱氢酶转化为乙酰辅酶A参与三羧酸循环，为细胞提供必需的能量。当细胞缺氧时，丙酮酸由胞质中的乳酸脱氢酶催化生成乳酸。乳酸不仅为线粒体呼吸提供能量源，还通过自分泌、旁分泌和内分泌等形式在炎症反应、创伤修复、记忆形成和神经保护以及肿瘤生长和转移等病理生理过程中发挥重要作用，影响疾病发展和预后。表观遗传修饰是通过修饰酶共价添加或水解组蛋白和DNA结构中的功能基团以调节基因复制、转录和翻译等过程，影响细胞生物学效应。组蛋白是真核生物染色体的基本结构蛋白，其翻译后修饰诸如甲基化、乙酰化等影响其与DNA双链的亲和性，改变染色质结构，广泛参与基因的表达调控。最新研究发现组蛋白上可以发生乳酰化修饰，即通过对组蛋白上的赖氨酸残基添加乳酸基团，使其作为一种全新的表观遗传修饰发挥作用。随着研究的深入，乳酰化修饰也被证明广泛发生在非组蛋白上。乳酰化修饰的发现扩大了对乳酸参与疾病病理机制的认识。该文主要综述了乳酰化修饰在肿瘤、炎性疾病和神经系统疾病中的作用和机制，以期为相关疾病的研究与诊疗提供新思路。

关键词: 乳酸, 乳酰化修饰, 肿瘤, 炎性疾病, 神经系统疾病

Abstract:

Lactic acid is a product of cell respiration. After entering into cells, glucose is metabolized to pyruvate by glycolysis. When the oxygen supply is sufficient, pyruvate is converted to acetyl coenzyme A through pyruvate dehydrogenase in the mitochondrial matrix to participate in the tricarboxylic acid cycle and provide necessary energy for cells. Pyruvate is catalysed by lactate dehydrogenase in the cytoplasm to produce lactate while cells are grown under hypoxic conditions. Lactate not only provides energy for mitochondrial respiration, but also plays important roles in inflammatory responser, wound repair, memory formation and neuroprotection as well as tumor growth and metastasis and other pathophysiological processes through autocrine, paracrine, and endocrine forms, which affects the development and prognosis of diseases. Epigenetic modification regulates gene replication, transcription and translation by covalently adding or hydrolyzing functional groups on histones and DNA through related enzymes and affects the biological effects of cells. Histones are the major structural proteins of eukaryotic chromosomes. Their post-translational modifications, such as methylation and acetylation, affect their affinity with DNA, change chromatin structures, and are widely involved in regulation of gene expression. Recent studies have found that histones can undergo lactylation, which is a new epigenetic modification by adding lactate to lysine residues on histones. As the research deepens, numerous evidences reveal that lactylation also occurs on non-histone proteins. The discovery of lactylation has expanded our understanding of lactate functions in the pathogenesis of diseases. In this review, we summarize the roles and mechanisms of lactylation in tumor, inflammatory and neural system diseases, in order to provide new ideas for the research, diagnosis and treatment of these diseases.

Key words: lactic acid, lactylation, tumor, inflammatory disease, neural system disease

中图分类号:

葛玲玲, 黄洪军, 罗艳. 乳酰化修饰在疾病中的作用及机制研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(3): 374-379.

GE Lingling, HUANG Hongjun, LUO Yan. Research progress in the role and mechanism of lactylation in diseases[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(3): 374-379.

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