Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Technologies Research Alliance, Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany.
Leibniz Institute for Plasma Science and Technology (INP), a member of the Leibniz Health Technologies Research Alliance, Felix-Hausdorff-Str. 2, 17489, Greifswald, Germany; Institute for Hygiene and Environmental Medicine, Greifswald University Medical Center, Sauerbruchstr., 17475, Greifswald, Germany.
Redox Biol. 2024 Nov;77:103343. doi: 10.1016/j.redox.2024.103343. Epub 2024 Sep 5.
Lipids, possessing unsaturated fatty acid chains and polar regions with nucleophilic heteroatoms, represent suitable oxidation targets for autologous and heterologous reactive species. Lipid peroxidation products (LPPs) are highly heterogeneous, including hydroperoxides, alkenals, chlorination, or glycation. Accordingly, delineation of lipid targets, species type, resulting products, and oxidation level remains challenging. To this end, liposomal biomimetic models incorporating a phosphatidylcholine, -ethanolamine, and a sphingomyelin were used to deconvolute effects on a single lipid scale to predict potential modification product outcomes. To introduce oxidative modifications, gas plasma technology, a powerful pro-oxidant tool to promote LPP formation by forming highly abundant reactive species in the gas and liquid phases, was employed to liposomes. The plasma parameters (gas type/combination) were modified to modulate the resulting species-profile and LPP formation by enriching specific reactive species types over others. HR-LC-MS (Münzel and et al., 2017) [2] was employed for LPP identification. Moreover, the heavy oxygen isotope O was used to trace O-incorporation into LPPs, providing first information on the plasma-mediated lipid peroxidation mechanism. We found that combination of lipid class and gas composition predetermined the type of attack: admixture of O to the plasma and the presence of nitrogen atoms with free electrons in the molecule lead to chlorination of the amide bond and headgroup. Here, atomic oxygen driven formation of hypochlorite is the major reactive species. In contrast, POPC yields mainly to LPPs with oxidation of the oleic acid tail, especially truncations, epoxidation, and hydroperoxide formation. Here, singlet oxygen is assumingly the major driver. O labelling revealed that gas phase derived reactive species are dominantly incorporated into the LPPs, supporting previous findings on gas-liquid interface chemistry. In summary, we here provided the first insights into gas plasma-mediated lipid peroxidation, which, employed in more complex cell and tissue models, may support identifying mechanisms of actions in plasma medicine.
脂质具有不饱和脂肪酸链和带有亲核杂原子的极性区域，是自体和异体反应性物质的合适氧化靶标。脂质过氧化产物（LPP）高度异质，包括过氧化物、烯醛、氯化或糖化。因此，脂质靶标、物种类型、产物和氧化水平的描绘仍然具有挑战性。为此，使用含有磷脂酰胆碱、-乙醇胺和神经鞘磷脂的脂质体仿生模型来对单个脂质尺度进行去卷积，以预测潜在的修饰产物结果。为了引入氧化修饰，采用气体等离子体技术，这是一种通过在气相和液相中形成大量丰富的反应性物质来促进 LPP 形成的强大促氧化剂工具，对脂质体进行处理。改变等离子体参数（气体类型/组合）以调节特定反应性物质类型的富集，从而调节所得物质谱和 LPP 形成。高分辨率 LC-MS（Münzel 等人，2017）[2]用于 LPP 鉴定。此外，重氧同位素 O 用于追踪 O 掺入 LPP 中，为血浆介导的脂质过氧化机制提供了第一手信息。我们发现，脂质类和气体组成的组合预先确定了攻击的类型：将 O 混入等离子体中，以及在分子中存在带自由电子的氮原子，导致酰胺键和头基的氯化。在这里，原子氧驱动次氯酸盐的形成是主要的反应性物质。相比之下，POPC 主要产生油酸尾氧化的 LPP，特别是截短、环氧化和过氧化物形成。在这里，单线态氧被认为是主要的驱动力。O 标记表明气相衍生的反应性物质主要掺入 LPP 中，这支持了先前关于气液界面化学的发现。总之，我们在此首次提供了关于气体等离子体介导的脂质过氧化的见解，该见解可用于更复杂的细胞和组织模型，以支持鉴定等离子体医学中的作用机制。
