The Altered Water System: Excess Levels of Free Radicals Contribute to Carcinogenesis by Altering Arginine Vasopressin Production and Secretion and Promoting Dysregulated Water Homeostasis in Concert with Other Factors
A large body of evidence accumulated during the last decade has revealed diverse roles of dysregulated water homeostasis in tumorigenesis. In particular, many tumors hypersecrete arginine vasopressin (AVP) causing hypoosmolar conditions associated with different cancers. Excess levels of free radicals and nonosmotic stimuli may act as signals in water homeostasis and induce the production and secretion of AVP. Hypoosmolar conditions cause alterations in the expression of many genes. Other alterations in hydration patterns may induce mutations and increase the levels of protein kinases to contribute to oncogenesis. Furthermore, AVP regulates the hypothalamic-pituitary-adrenal axis and angiogenesis, and its overproduction may contribute to tumor growth and metabolism. This review article describes a mechanism by which oxygen radical species and other free radicals act as signaling molecules that, in concert with increased AVP production and secretion, pleiotropically affect tumor growth and metabolism, resulting in dysregulated proliferation, cell cycle arrest, apoptosis, and genomic instability. 1. Introduction Previously unrecognized vital roles of water in the body have been uncovered during the last decade [1, 2]. In the case of humans, water molecules are hypothesized to behave as a “molecular supercomputer” that interprets and reacts to biochemical pathways in accordance with prevailing demands to achieve homeostasis through complex signaling pathways that are referred to as the “water governing cycle” [2]. Plants possess complex signaling pathways that are highly adaptable because of their ability to interpret and react to stressors such as osmotic fluctuations and the overabundance of saline by rapidly altering gene expression that corresponds to biochemical and physiological alterations, even under mild conditions, to achieve homeostasis [3–5]. However, limited research has addressed whether osmotic fluctuations rapidly alter gene expression in accordance with prevailing demands in animals and humans. For example, research on animals has shown that sustained hypoosmolar (excess water relative to solute molecules) or hyperosmolar conditions (water deficiency relative to solute molecules) significantly alter the expression of a wide variety of regulatory genes in a global but selective manner [6, 7]. Moreover, water molecules contribute to specific and nonspecific binding of peptides to proteins [1, 8], may play a significant role in mediating sequence-specific recognition, and increase the affinity of proteins for DNA [9–15]. The role of water in
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