Vo Anh T T, Khan Uffaf, Liopo Anton V, Mouli Karthik, Olson Kenneth R, McHugh Emily A, Tour James M, Pooparayil Manoj Madhavan, Derry Paul J, Kent Thomas A
Center for Genomics and Precision Medicine, Institute of Bioscience and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
Department of Chemistry, Rice University, Houston, TX 77005, USA.
Nanomaterials (Basel). 2024 Dec 13;14(24):2007. doi: 10.3390/nano14242007.
Harsh acid oxidation of activated charcoal transforms an insoluble carbon-rich source into water-soluble, disc structures of graphene decorated with multiple oxygen-containing functionalities. We term these pleiotropic nano-enzymes as "pleozymes". A broad redox potential spans many crucial redox reactions including the oxidation of hydrogen sulfide (HS) to polysulfides and thiosulfate, dismutation of the superoxide radical (O*), and oxidation of NADH to NAD. The oxidation of HS is predicted to enhance protein persulfidation-the attachment of sulfur to cysteine residues. Persulfidated proteins act as redox intermediates, and persulfidation protects proteins from irreversible oxidation and ubiquitination, providing an important means of signaling. Protein persulfidation is believed to decline in several neurological disorders and aging. Importantly, and consistent with the role of persulfidation in signaling, the master antioxidant transcription factor Nrf2 is regulated by Keap1's persulfidation. Here, we demonstrate that pleozymes increased overall protein persulfidation in cells from apparently healthy individuals and from individuals with the mitochondrial protein mutation responsible for Friedreich's ataxia. We further find that pleozymes specifically enhanced Keap1 persulfidation, with subsequent increased accumulation of Nrf2 and Nrf2's antioxidant targets.
活性炭的强酸性氧化将一种不溶性的富碳源转化为水溶性的、具有多种含氧官能团修饰的石墨烯盘状结构。我们将这些具有多种功能的纳米酶称为“多酶”。一个宽泛的氧化还原电位涵盖了许多关键的氧化还原反应，包括硫化氢（HS）氧化为多硫化物和硫代硫酸盐、超氧自由基（O*）的歧化反应以及NADH氧化为NAD。预计HS的氧化会增强蛋白质的过硫化作用——硫与半胱氨酸残基的结合。过硫化蛋白质作为氧化还原中间体，而过硫化作用可保护蛋白质免受不可逆氧化和泛素化，提供一种重要的信号传导方式。据信，蛋白质过硫化作用在几种神经疾病和衰老过程中会下降。重要的是，与过硫化作用在信号传导中的作用一致，主要抗氧化转录因子Nrf2受Keap1的过硫化作用调节。在这里，我们证明多酶增加了来自表面健康个体以及患有导致弗里德赖希共济失调的线粒体蛋白突变个体的细胞中的总体蛋白质过硫化作用。我们进一步发现，多酶特异性增强了Keap1的过硫化作用，随后Nrf2及其抗氧化靶点的积累增加。
