Impact of Non-Invasive Physical Plasma on Heat Shock Protein Functionality in Eukaryotic Cells

Abstract

Recently, biomedical research has increasingly investigated physical plasma as an innovative therapeutic approach with a number of therapeutic biomedical effects. It is known from radiation and chemotherapy that these applications can lead to the induction and activation of primarily cytoprotective heat shock proteins (HSP). HSP protect cells and tissues from physical, (bio)chemical, and physiological stress and, ultimately, along with other mechanisms, govern resistance and treatment failure. These mechanisms are well known and comparatively well studied in drug therapy. For therapies in the field of physical plasma medicine, however, extremely little data are available to date. In this review article, we provide an overview of the current studies on the interaction of physical plasma with the cellular HSP system.

Keywords: cellular stress; cold atmospheric plasma; cold atmospheric pressure plasma; cold plasma; tissue tolerable plasma.

Figure 1

Heat shock proteins (HSP) are substantial cellular regulators of the eukaryotic stress response. HSP are named according to their molecular weights. The major members of the HSP superfamily are classified as HSP27, HSP40, HSP60, HSP70 and HSP90. Heat shock transcription factor 1 (HSF1) is considered the central factor of HSP expression. HSP mediate inducible protective mechanisms against chemical and physical noxae, including chemical and physical therapy approaches. HSP also exhibit cytoprotective and thus prooncogenic effects in tumor diseases and the interaction of cancer cells with the microenvironment and tumor-associated components of the immune system. At the molecular level, HSP control the correct folding of proteins, but also determine their stability and turnover, and thus the functionality of protein factors in cell physiology. For details, please refer to the text.

Figure 2

Non-invasive physical plasma (NIPP) treatment introduces reactive oxygen species (ROS) such as ozone (O₃), superoxide anion (O₂⁻•), and hydroxyl radical (OH⁻•) into the tissue. Within the cells, a stress-induced response of the heat shock protein (HSP) system occurs. Mediated by transcriptionally active heat shock factor-1 (HSF-1), HSP27 and HSP60 are induced, partially phosphorylated (pHSP27), and secreted (sHPS27), controlling cytoskeletal and mitochondrial functionality. Furthermore, large HSP70 and HSP90 and the co-chaperone HSP40 are activated. As part of the NIPP effect, HSP90 can also be cleaved and thus inactivated. Cell responses controlled by HSP include morphology, motility, cytoprotection and, depending on the redox state, apoptosis and cell death.