Laboratorio de Biologia Vascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Laboratorio de Biologia Vascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
Clin Sci (Lond). 2018 Jun 21;132(12):1257-1280. doi: 10.1042/CS20180157. Print 2018 Jun 29.
Thiol groups are crucially involved in signaling/homeostasis through oxidation, reduction, and disulphide exchange. The overall thiol pool is the resultant of several individual pools of small compounds (e.g. cysteine), peptides (e.g. glutathione), and thiol proteins (e.g. thioredoxin (Trx)), which are not in equilibrium and present specific oxidized/reduced ratios. This review addresses mechanisms and implications of circulating plasma thiol/disulphide redox pools, which are involved in several physiologic processes and explored as disease biomarkers. Thiol pools are regulated by mechanisms linked to their intrinsic reactivity against oxidants, concentration of antioxidants, thiol-disulphide exchange rates, and their dynamic release/removal from plasma. Major thiol couples determining plasma redox potential () are reduced cysteine (CyS)/cystine (the disulphide form of cysteine) (CySS), followed by GSH/disulphide-oxidized glutathione (GSSG). Hydrogen peroxide and hypohalous acids are the main plasma oxidants, while water-soluble and lipid-soluble small molecules are the main antioxidants. The thiol proteome and thiol-oxidoreductases are emerging investigative areas given their specific disease-related responses (e.g. protein disulphide isomerases (PDIs) in thrombosis). Plasma cysteine and glutathione redox couples exhibit pro-oxidant changes directly correlated with ageing/age-related diseases. We further discuss changes in thiol-disulphide redox state in specific groups of diseases: cardiovascular, cancer, and neurodegenerative. These results indicate association with the disease states, although not yet clear-cut to yield specific biomarkers. We also highlight mechanisms whereby thiol pools affect atherosclerosis pathophysiology. Overall, it is unlikely that a single measurement provides global assessment of plasma oxidative stress. Rather, assessment of individual thiol pools and thiol-proteins specific to any given condition has more solid and logical perspective to yield novel relevant information on disease risk and prognosis.
巯基在氧化、还原和二硫键交换过程中对信号转导/动态平衡起着至关重要的作用。总巯基池是由几种小分子化合物（如半胱氨酸）、肽（如谷胱甘肽）和巯基蛋白（如硫氧还蛋白 (Trx)）组成的特定氧化/还原比例的个体池的结果。本文综述了循环血浆巯基/二硫键氧化还原池的机制和意义，这些机制参与了几种生理过程，并被探索作为疾病生物标志物。巯基池的调节机制与其对氧化剂的固有反应性、抗氧化剂的浓度、巯基-二硫键交换速率以及它们从血浆中的动态释放/清除有关。决定血浆氧化还原电势 ( ) 的主要巯基对是还原型半胱氨酸 (CyS)/半胱氨酸二硫化物 (半胱氨酸的二硫化物形式) (CySS)，其次是谷胱甘肽/二硫化物-氧化型谷胱甘肽 (GSSG)。过氧化氢和次卤酸是主要的血浆氧化剂，而水溶性和脂溶性小分子是主要的抗氧化剂。由于其与特定疾病相关的反应（例如血栓形成中的蛋白质二硫键异构酶 (PDIs)），巯基蛋白质组和巯基氧化还原酶是新兴的研究领域。血浆半胱氨酸和谷胱甘肽氧化还原对的促氧化剂变化与衰老/衰老相关疾病直接相关。我们进一步讨论了特定疾病组中巯基-二硫键氧化还原状态的变化：心血管疾病、癌症和神经退行性疾病。这些结果表明与疾病状态有关，尽管还没有明确到产生特定的生物标志物。我们还强调了巯基池影响动脉粥样硬化病理生理学的机制。总的来说，单一测量不太可能提供对血浆氧化应激的全面评估。相反，对任何特定条件下的个体巯基池和巯基蛋白的评估更具有坚实和合乎逻辑的视角，可以提供关于疾病风险和预后的新的相关信息。
