Effect of highly mineralized natural water on redox processes in HaCaT keratinocytes.

Research Center of Clinical and Experimental Medicine, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk, Russia. Address for correspondence: natasha115@list.ru. N. S. Zaitseva Previous studies have demonstrated that highly mineralized natural water (brine solutions) induces differentiation of HaCaT keratinocytes and modulates cell cycle dynamics [1], which implies the involvement of various regulatory system of the cell. An important role in differentiation of epidermal keratinocytes is played by ROS that initiate the key processes related to cell cycle arrest and elimination of cellular organelles during differentiation [6]. ROS are generated by mitochondrial electron transporting complexes I and III. This process is controlled by a number of factors affecting both ROS generation and elimination [3]. Changes in the ionic composition of the environment and cell dehydration under hyperosmotic conditions can induce ROS hyperproduction by mitochondria [4] and produce a destructive effect on cells. An important role in elimination of ROS excess is played by redox-sensitive transcription factor Nrf2 and Nrf2-related genes under ARE promoter (antioxidant responsive element) encoding antioxidant enzymes of the cell [2,9]. The correlation of hyperosmotic stress with enhanced production of mitochondrial ROS is described for yeasts [7], but was not demonstrated in mammalian cells. However, hyperosmotic sorbitol exposure on 3T3 and Jurkat cells induces rapid and reversible dissipation of mitochondrial proton gradient [5]. Here we studied the effect of hyperosmotic brine solution (BS) on mitochondrial potential, ROS production, and activation of transcription factor Nrf2 in HaCaT cells.