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- ItemCan the effect of cold physical plasma-derived oxidants be transported via thiol group oxidation?(Amsterdam [u.a.] : Elsevier, 2019) Heusler, Thea; Bruno, Giuliana; Bekeschus, Sander; Lackmann, Jan-Wilm; Woedtke, Thomas von; Wende, KristianPurpose: Intra- and intercellular redox-signaling processes where found responsible in various physiological and pathological processes with cellular thiol groups as important signal transducers. Using cold atmospheric plasma (CAP), a similar oxidation pattern of thiol groups can be achieved. Hence, it must be clarified which role extracellular thiol groups play in mediating CAP effects and whether or not the effects of short-lived reactive species can be preserved in a molecule like cysteine. Methods: Physiological buffer solutions containing the amino acid cysteine were treated by an MHz argon plasma jet with molecular gas admixtures (kINPen) and transferred to cultured human keratinocytes. Cell proliferation, migratory activity, and metabolism were investigated. High-resolution mass spectrometry was used to estimate the impact of plasma generated species on thiol groups. Results: While treated physiologic cysteine concentrations showed no impact on cell behavior, artificially high concentrations decreased proliferation, migration and lactate secretion. GSH levels inside cells were stabilized. Conclusion: Extracellular thiol groups scavenge plasma-generated species and form a multitude of covalent modifications. Unexpectedly, human keratinocytes show only small functional consequences for treated physiologic cysteine concentrations. Results for high concentrated cysteine solutions indicate an improved cytostatic/cytotoxic impact by plasma treatment suggesting a potential application as a “preserving agent” of the chemical energy of plasma-derived species. © 2019 The Authors
- ItemCell cycle-related genes associate with sensitivity to hydrogen peroxide-induced toxicity(Amsterdam [u.a.] : Elsevier, 2022) Bekeschus, Sander; Liebelt, Grit; Menz, Jonas; Singer, Debora; Wende, Kristian; Schmidt, AnkeReactive oxygen species (ROS) such as hydrogen peroxide (H2O2) are well-described agents in physiology and pathology. Chronic inflammation causes incessant H2O2 generation associated with disease occurrences such as diabetes, autoimmunity, and cancer. In cancer, conditioning of the tumor microenvironment, e.g., hypoxia and ROS generation, has been associated with disease outcomes and therapeutic efficacy. Many reports have investigated the roles of the action of H2O2 across many cell lines and disease models. The genes predisposing tumor cell lines to H2O2-mediated demise are less deciphered, however. To this end, we performed in-house transcriptional profiling of 35 cell lines and simultaneously investigated each cell line's H2O2 inhibitory concentration (IC25) based on metabolic activity. More than 100-fold differences were observed between the most resistant and sensitive cell lines. Correlation and gene ontology pathway analysis identified a rigid association with genes intertwined in cell cycle progression and proliferation, as such functional categories dominated the top ten significant processes. The ten most substantially correlating genes (Spearman r > 0.70 or < -0.70) were validated using qPCR, showing complete congruency with microarray analysis findings. Western blotting confirmed the correlation of cell cycle-related proteins negatively correlating with H2O2 IC25. Top genes related to ROS production or antioxidant defense were only modest in correlation (Spearman r > 0.40 or < -0.40). In conclusion, our in-house transcriptomic correlation analysis revealed a set of cell cycle-associated genes associated with a priori resistance or sensitivity to H2O2-induced cellular demise with the detailed and causative roles of individual genes remaining unclear.