ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), Felix-Hausdorff-Straße 2, 17489 Greifswald, Germany.
Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Joseph-Stelzmann-Straße 26, 50931 Cologne, Germany.
Biointerphases. 2020 Nov 25;15(6):061008. doi: 10.1116/6.0000529.
Cold physical plasmas are emerging tools for wound care and cancer control that deliver reactive oxygen species (ROS) and nitrogen species (RNS). Alongside direct effects on cellular signaling processes, covalent modification of biomolecules may contribute to the observed physiological consequences. The potential of ROS/RNS generated by two different plasma sources (kINPen and COST-Jet) to introduce post-translational modifications (PTMs) in the peptides angiotensin and bradykinin was explored. While the peptide backbone was kept intact, a significant introduction of oxidative PTMs was observed. The modifications cluster at aromatic (tyrosine, histidine, and phenylalanine) and neutral amino acids (isoleucine and proline) with the introduction of one, two, or three oxygen atoms, ring cleavages of histidine and tryptophan, and nitration/nitrosylation predominantly observed. Alkaline and acidic amino acid (arginine and aspartic acid) residues showed a high resilience, indicating that local charges and the chemical environment at large modulate the attack of the electron-rich ROS/RNS. Previously published simulations, which include only OH radicals as ROS, do not match the experimental results in full, suggesting the contribution of other short-lived species, i.e., atomic oxygen, singlet oxygen, and peroxynitrite. The observed PTMs are relevant for the biological activity of peptides and proteins, changing polarity, folding, and function. In conclusion, it can be assumed that an introduction of covalent oxidative modifications at the amino acid chain level occurs during a plasma treatment. The introduced changes, in part, mimic naturally occurring patterns that can be interpreted by the cell, and subsequently, these PTMs allow for prolonged secondary effects on cell physiology.
冷等离子体作为伤口护理和癌症控制的新兴工具，能够递送活性氧（ROS）和活性氮（RNS）。除了对细胞信号转导过程的直接影响外，生物分子的共价修饰也可能导致观察到的生理后果。本研究探索了两种不同等离子体源（kINPen 和 COST-Jet）产生的 ROS/RNS 对血管紧张素肽和缓激肽肽引入翻译后修饰（PTMs）的潜力。虽然肽骨架保持完整，但观察到显著的氧化 PTM 引入。修饰主要发生在芳香族（酪氨酸、组氨酸和苯丙氨酸）和中性氨基酸（异亮氨酸和脯氨酸）上，引入一个、两个或三个氧原子、组氨酸和色氨酸的环裂解，以及主要观察到的硝化/亚硝化。碱性和酸性氨基酸（精氨酸和天冬氨酸）残基表现出很高的抗性，表明局部电荷和大的化学环境调节富含电子的 ROS/RNS 的攻击。先前的模拟研究仅包括 OH 自由基作为 ROS，但不完全符合实验结果，这表明其他短寿命物质（即原子氧、单线态氧和过氧亚硝酸盐）的贡献。观察到的 PTMs 与肽和蛋白质的生物学活性相关，改变了极性、折叠和功能。总之，可以假设在等离子体处理过程中，氨基酸链水平上会发生共价氧化修饰的引入。引入的变化部分模拟了细胞可以解释的天然存在模式，随后，这些 PTMs 允许对细胞生理学产生延长的次级影响。
