Abstract
Non-thermal plasma (NTP), the fourth state of matter, holds promise in altering biological matter, particularly in cancer treatment. NTP influences cell signaling by modifying key components, such as membranes, proteins, and DNA. It selectively targets cancer cells through the generation of reactive oxygen and nitrogen species (RONS), which modify amino acids within proteins. Understanding these molecular mechanisms is vital for optimizing NTP's potential in oncology. This book chapter reviews recent computer simulations and experimental findings exploring NTP's impact on proteins in cancer therapy, providing insights into how protein modifications affect cancer cell behavior and therapy responses. This knowledge advances NTP-based cancer treatments, offering the potential for personalized and targeted therapies in the future.
Top2. Post-Translational Modifications And Their Impact On Catalytic Proteins
Proteins, particularly catalytic ones, play vital roles in various biochemical reactions and cellular pathways (Alberts, 2017). Their functionality can be affected by various internal and external factors, with RONS being one of the most significant external influencers (Dröge, 2002). This section sheds light on the effects of RONS on several catalytic proteins (Halliwell, 2006), particularly focusing on cytoglobin, catalase, peroxidase, and SOD, detailing their structure, function, and interactions under various conditions. Cytoglobin (CYGB) is a relatively newly discovered globin proposed to play a role in cellular protection against oxidative stress (Burmester et al., 2002; De Backer et al., 2018). One of the emerging tools in cancer therapy is NTP, which primarily generates RONS (Fridman et al., 2008). The interaction of these RONS with cellular proteins, especially redox-regulatory ones like CYGB, can determine the cell's fate (Smith et al., 2010). NTP treatment on CYGB has shown that while the protein undergoes chemical modifications, its secondary structure remains largely unaffected (De Backer et al., 2018). Spectroscopic analysis revealed the oxidations to mainly occur in sulfur-containing and aromatic amino acids (Stadtman & Levine, 2003). With prolonged NTP exposure, nitration of the heme group in CYGB was also observed. Furthermore, the two surface-exposed cysteine residues in CYGB were oxidized, leading to the formation of both intermolecular and potential intramolecular disulfide bridges.
Figure 1. The binding hotspot of CYGBSH-SH is illustrated in panels (a-b), while panels (c-d) depict CYGBS-S, with these regions shown as red meshed areas. To enhance clarity, the helices within the structures are represented in subtle, pale colors. The heme group and specific histidine residues (81, 113, 117) are given in green and light purple, with licorice-style representations. It's evident that the access to the heme group is notably increased in CYGBS-S compared to CYGBSH-SH.
Key Terms in this Chapter
RONS: Reactive Oxygen and Nitrogen Species
GSH: Glutathione
SIRPa: Signal-Regulatory Protein Alpha
hEGF: Human Epidermal Growth Factor
CD44: Cluster Of Differentiation 44
AQPs: Aquaporins
CYGB: Cytoglobin
ROS: Reactive Oxygen Species
RNS: Reactive Nitrogen Species
FEP: Free Energy Profile
GPX4: Glutathione Peroxidase 4