Privolzhsky Research Medical University,Russia
Title: Hemoproteins and Elemental Homeostasis in Brain Tumors: Looking Inside the Pathways
A. B. Yazykova working at Federal State Budgetary Educational Institution of Higher Education “Privolzhsky Research Medical University” of the Ministry of Health of the Russian Federation, Nizhny Novgorod, Russia
The National Center for Biotechnological Information (NCBI) defines bioinformatics as a field of science in which biology, informatics and information technology merge into a single discipline. In bioinformatics there are three important sub-disciplines, such as the development of new algorithms and statistics, through which it is possible to evaluate the relationships between members of large data sets; analysis and interpretation of various types of data, including nucleotide and amino acid sequences, protein domains and protein structures; as well as the development and implementation of tools that provide effective access to and management of various types of information. An effective way to analyse metabolic changes is to build signal networks. The signal network is a probabilistic model of the transmission of a stream of biological information in a cell and between cells, tissues and organs through interactions of cellular agents of different origin. The structural element of the signal network is the binary interaction between two elementary objects. A higher-level component is a signal cascade or path represented by a set of consecutive interactions of partner molecules from the incoming signal to the final reaction associated with the initiation of a specific biological process: activation of gene group expression, opening of ion channels, assembly / disassembly and contraction of the cell cytoskeleton, division, apoptosis etc. The main elements of signalling pathways are proteins, since they are the main regulators of cell activity.
Primary tumors of central nervous system are a rare group of diverse tumors that account for less than 2% of all tumors, but are the fourth most common cause of cancer death. Despite of advances in neurosurgery, the development of intraoperative navigation, as well as chemo and radiation therapy, treatment of primary central nervous system tumors is still insufficiently effective.In the present study, the aim was to investigate blood and tissue macroelements, microelements and hemoproteins level in brain tumors, as well as their intermolecular interactions.
Results and discussion.
Modern databases of signaling pathways (KEGG) suggest that in normal cells the conditions of hypoxia can lead to HIF-1A protein synthesis. Besides, it is known, that chronic intermittent hypoxia (CIH) induces reactive oxygen species (ROS) generation, thereby increasing HIF-1 α expression. Detected reduced magnesium content in brain cancer cells can lead to decreasing of HIF-1 α activation, and probably, can serve as initiating agent for pathologic proliferation development. This factor, together with the protein p53 leads to synthesis and activation of proteins p21/27, which in turn inhibits CDK4/6 and leads to proliferation decrease. Intermittent hypoxia, leading to activation of the NOX enzyme, activates ROS synthesis, which inhibits the PHD enzyme and triggers the release of calcium ions. Calcium ions can be a triggering factor of two fundamental processes, apoptosis (often implemented under normal conditions) and cell proliferation via the Ras protein. In glioma activation of protein synthesis of EGFR was shown, which, presumably, dramatically increases the release of calcium and thus activates the Ras protein, triggering uncontrolled proliferation. The effects of ROS on the release of calcium ions (Figure 1) may exacerbate this effect. There is evidence that under hypoxic conditions the cell produces myoglobin, which inactivates tumor growth and represents a factor of the cells adaptation to hypoxia. According to the literature a hypothetical relationship with MB is noted, as well as the expression of catalase, reduction of free radicals and oxidative stress
This is one of the first studies to have examined intermolecular relationships between microelements, hemoproteins and antioxidant enzymes in gliomas. In hypomagnesemia, observed in cancer cells, HIF-1 α stabilization and activation by ROS is violated, and that leads to activation of cell pathological proliferation. Under the circumstances, increased Ca concentration via Ras-way activation leads to cell proliferation activation, more aggravating the situation. Combined disruption of mineral homeostasis and hypoxia, found in the present study, also can serve as factors, stimulating cell proliferation. Established increasing of hemoproteins activity, such as catalase and myoglobin, can possibly be considered as adaptation factor towards hypoxia, oxidative stress and element homeostasis violation.