Department of Glyco-Oncology and Medical Biochemistry, Research Center, Osaka International Cancer Institute, Osaka, Japan.
Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan.
Antioxid Redox Signal. 2024 Nov;41(13-15):910-926. doi: 10.1089/ars.2024.0774.
Reduction-oxidation (redox) regulation is an important biological phenomenon that provides a balance between antioxidants and the generation of reactive oxygen species and reactive nitrogen species under pathophysiological conditions. Structural and functional changes in glycans are also important as post-translational modifications of proteins. The integration of glycobiology and redox biology, called glyco-redox has provided new insights into the mechanisms of epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET), cancer, and various diseases including Alzheimer's disease, chronic obstructive lung disease, type 2 diabetes, interstitial pneumonitis, and ulcerative colitis. Glycans are biosynthesized by specific glycosyltransferases and each glycosyltransferase is either directly or indirectly regulated by oxidative stress and redox regulation. A typical example of glyco-redox is the role of N-glycan referred to as core fucose in superoxide dismutase 3. This glycan was found to be involved in the growth inhibition of cancer cell lines. The significance of glyco-redox in EMT/MET, cancer, and various diseases was found in major N-glycan branching glycosyltransferases β1,4N-acetylglucosaminyltransferase III, β1,4N-acetylglucosaminyltransferase IV, β1,6N-acetylglucosaminyltransferase V, β1,4-acetylglucosaminyltransfearfse VI, β1,6-acetylglucosaminyltransferase IX, α-1,6 fucosyltransferase, and β-galactoside α-2,6-sialyltransferase 1. Herein, we summarize previous reports on target proteins and how this relates to oxidative stress. We also discuss the products of these processes and their significance to cancer and various diseases. A clear-cut understanding of the significance of glyco-redox in relation to prevention, diagnosis, and therapeutics is required. These studies will open a new road toward glycobiology and redox biology. 41, 910-926.
氧化还原（redox）调节是一种重要的生物学现象，它在病理生理条件下提供了抗氧化剂和活性氧（ROS）和活性氮（RNS）产生之间的平衡。糖链的结构和功能变化也是蛋白质翻译后修饰的重要方式。糖生物学和氧化还原生物学的结合，称为糖氧化还原，为上皮-间充质转化（EMT）/间充质-上皮转化（MET）、癌症以及包括阿尔茨海默病、慢性阻塞性肺病、2 型糖尿病、间质性肺炎和溃疡性结肠炎在内的各种疾病的机制提供了新的见解。糖链是由特定的糖基转移酶生物合成的，每个糖基转移酶都直接或间接地受到氧化应激和氧化还原调节的调节。糖氧化还原的一个典型例子是 N-糖链（称为超氧化物歧化酶 3 的核心岩藻糖）的作用。该糖链被发现参与了癌细胞系的生长抑制。在 EMT/MET、癌症和各种疾病中，糖氧化还原的意义在于主要的 N-糖链分支糖基转移酶β1,4N-乙酰氨基葡萄糖基转移酶 III、β1,4N-乙酰氨基葡萄糖基转移酶 IV、β1,6N-乙酰氨基葡萄糖基转移酶 V、β1,4-乙酰氨基葡萄糖基转移酶 VI、β1,6-乙酰氨基葡萄糖基转移酶 IX、α-1,6 岩藻糖基转移酶和β-半乳糖苷α-2,6-唾液酸基转移酶 1。本文总结了以前关于靶蛋白的报道以及这与氧化应激的关系。我们还讨论了这些过程的产物及其对癌症和各种疾病的意义。需要明确理解糖氧化还原在预防、诊断和治疗中的意义。这些研究将为糖生物学和氧化还原生物学开辟新的道路。41, 910-926。
