The Role Of Cytoglobin In The Plasma-Treatment Of Melanoma

Abstract

Globins are ancient proteins that are present in all kingdoms of life. At the moment, there are 8 different globins known in vertebrates with distinct expression patterns. Human cytoglobin (CYGB), a member of this globin superfamily, is a hexacoordinated heme-protein that is mostly expressed in fibroblasts and fibroblast-related cells, but is also present in neurons, macrophages, muscles and epithelium. Although globins can have a respiratory function, additional functions such as roles in NO metabolism, signal transduction, lipid metabolism and the detoxification of ROS have been proposed. As a consequence of these different functions and localisations, Cygb probably plays a significant role in different pathological conditions such as fibrosis, neurodegeneration and tumorigenesis. For the latter, CYGB has been proposed to be a candidate tumour-suppressor gene [1] as its downregulation in tumors has been associated with increased cancer cell proliferation and elevated extracellular signalregulated kinase and Akt activation [2]. It has been shown that the highest Cygb expression is seen in melanocytes [3]. Furthermore, melanocyte to melanoma transition has been associated with DNAmethylation induced reduction of Cygb expression. While melanoma is accounting for We have studied the effect of CAP on the cell viability of two melanoma cell lines and on melanocytes and investigated the role of Cygb herin. Furthermore as it is hypothesized that Cygb can act as a ROS regulator/scavanger, the intracellular ROS concentration was measured in the different cell lines. The observed results indicate a correlation between the expression level of Cygb, the intracellular ROS concentration and the sensitivity of the cell line towards CAP treatment. The molecular mechanism of how Cygb exerts its effect is however, unclear. Therefore we have performed spectroscopic and simulation studies to determine the effect of CAP on the structure of Cygb. Hopefully, this investigation of the combined effect of CAP treatment on cell viability and the (possible) role of Cygb as ROS scavenger and its structural effect, may contribute to the characterization of the biochemical pathways underlying the response of melanocytes and melanomas to CAP treatment.