CELL REDOX HOMEOSTASIS

Abstract

Dear Editor-in-Chief: One of the intriguing questions in the field of redox biology of exercise is whether blood regulates tissue redox homeostasis. At present, the idea prevailing in the field is that blood plasma is largely considered an inert body fluid, a kind of “sink” that passively accepts reactive species and oxidative products produced mainly from exercising skeletal muscles (3). In our opinion, however, this frequently adopted cell- and muscle-centric point of view has not been put into a rigorous test whatsoever. Recent evidence by Conti et al. (1) is now challenging this notion. Using a novel approach, the researchers conditioned endothelial cells with sera from triathletes (“aerobic” activity), sprint runners (“anaerobic” activity), and soccer players (mixed “aerobic–anaerobic” activity) and examined the effects of these sera on several parameters related to redox homeostasis in endothelial cells. Although apparently, it was not one of the aims of these researchers, we believe that their innovative cell culture setup provides promising evidence to support the possible regulatory role of blood plasma on cell and tissue redox homeostasis. Conti et al. (1) reported that both primary and cell line endothelial cells incubated with blood serum (instead of fetal bovine serum as it is usually the case) and exposed or not to oxidative stress induced by hydrogen peroxide have provoked several changes in redox homeostasis in endothelial cells. Indeed, messenger RNA levels and activity of catalase in endothelial cells varied in most cases among the cells treated with sera from athletes participating in different types of sports. In addition, induction of oxidative stress in the cell culture medium increased catalase activity only in cells treated with sera from soccer players and triathletes but not from sprint runners. Likewise, incubation of endothelial cells with human sera from sprint runners but not from soccer players and triathletes increased the NAD+/NADH ratio (one of the master redox potential regulators of the cell [2]). Moreover, induction of oxidative stress increased the NAD+/NADH ratio only in cells treated with sera from soccer players. On the basis of this evidence, it is inferred that these changes in redox homeostasis are strongly dependent on the type of sport practiced by the volunteers who provided the sera. Application of this original in vitro–in vivo technique (i.e., cultured cells incubated with fresh human serum) provided probably for the first time direct evidence that human serum strongly affects redox homeostasis of endothelial cells and that these effects are, to a great extent, dependent on the exercise training stimulus. The choice of endothelial cells is critical, considering the direct contact of blood plasma with endothelial cells, increasing the physiological implications of this in vitro model. The role of blood in reactive species biology has perhaps not received the attention it deserves. Importantly, this study lends support to the hypothesis that at least some of the effects of exercise on tissue redox homeostasis are partially due to changes in the molecular composition of blood plasma. Undoubtedly, the search for the circulating factors responsible for these effects on cell redox homeostasis and the need for techniques more applicable to the in vivo state would be a fruitful area of research. Michalis G. Nikolaidis, PhD Antonios Kyparos, PhD Ioannis S. Vrabas, PhD Laboratory of Exercise Physiology and Biochemistry Department of Physical Education and Sport Sciences at Serres Aristotle University of Thessaloniki Serres, Greece The authors declare no conflicts of interest.