Systemic hypoxia promotes lymphocyte apoptosis induced by oxidative stress during moderate exercise

Abstract

Blood undergoes oxidative stress during severe hypoxia or intense exercise. Excessive exposure to oxidative stress induces replicative senescence and apoptosis of lymphocytes. This study determines how various exercises with/without hypoxia affect lymphocyte subset mobilization and oxidative stress-induced lymphocyte apoptosis. Eighteen sedentary males randomly engaged in two normoxic exercise bouts [severe exercise (SE) (up to VO(2max)) and moderate-intensity exercise (ME) (50%VO(2max)) while exposed to 21%O(2)], two hypoxic exercise bouts (ME while exposed to 12%O(2) and 15%O(2)) and two hypoxic resting conditions (resting while exposed to 12%O(2) and 15%O(2)) in a normobaric hypoxia chamber. Under normoxic conditions, SE but not ME (1) increased the percentages of senescent (CD28(-) and CD57(+))/activated (CD62L(-) and CD11a(+))-form lymphocytes mobilized into the peripheral blood compartment; (2) decreased the levels of surface thiol and intracellular total (t-GSH) and reduced-form glutathione (r-GSH) of lymphocytes in blood; and (3) further enhanced the extents of H(2)O(2)-induced mitochondria trans-membrane potential diminishing, caspases 3/8/9 activation, poly(ADP-ribose) polymerase cleavage and phosphotidyl serine exposure in blood lymphocytes. However, no significant change occurred in the subset mobilization, antioxidant levels or apoptosis of lymphocytes following exposure to either 12%O(2) or 15%O(2). Although both 12%O(2) and 15%O(2) ME increased the mobilization of senescent/activated-form lymphocytes, only 12%O(2) ME enhanced H(2)O(2)-induced lymphocyte thiol, t-GSH and r-GSH consumption and apoptotic responses. Therefore, we conclude that the 12%O(2) exposure increases the mobilization of senescent/activated-form lymphocytes into the peripheral blood compartment and simultaneously enhances oxidative stress-induced lymphocyte apoptosis by diminishing cellular antioxidant levels during exercise.

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers

“…A previous study in male subjects reports that acute hypoxemia produced by inhalation of a hypoxic gas mixture does not modify the production of reactive species and oxidative stress either at rest or after static handgrip at 60% of maximal voluntary contraction until exhaustion (Dousset et al 2002). However, other investigations showing almost unanimously that environmentally induced hypoxemia (i.e, due to reduced partial pressure of oxygen in the air inspired) induced oxidative stress both at rest and after exercise (Joanny et al 2001;Pialoux et al 2009Pialoux et al , 2010Vasankari et al 1997;Wang et al 2007;Wang and Lin 2010). It has been recently demonstrated that elite athletes who lived in hypoxemic conditions and were aerobically trained for 18 days under normoxemic conditions (''live high-train low'' method), magnified the exercise-induced decrease in antioxidant status that normally observed when athletes live and train in normoxemic conditions (''live low-train Training experience (y) 5.8 ± 1.2 4.9 ± 0.5 _ VO 2max (ml kg -1 min -1 ) 62.0 ± 1.9 60.5 ± 2.2…”

“…It has been hypothesized that this increased production of reactive species during hypoxia exposure is, at least partly, the cause of hypoxemia and the resulting decline in physical ability (Guenette and Sheel 2007;Nielsen 2003). There is significant number of studies that have investigated the effect of high altitude-induced hypoxia on oxidative stress at rest and after exercise (Joanny et al 2001;Pialoux et al 2009Pialoux et al , 2010Vasankari et al 1997;Wang et al 2007;Wang and Lin 2010). Nevertheless, to our knowledge, no study has tested whether EIAH, that is hypoxemia elicited by exercise itself at a sea level, is accompanied by changes in redox status.…”

Hypoxic training: Clinical benefits on cardiometabolic risk factors

“…The increase in both SBP and DBP at higher altitudes may be attributed by the higher hypoxic stress imposed on the body, causing heightened sympathetic responses including increased secretion of hormones like epinephrine and noradrenaline [14,35]. However, it was theorized [36] that this response may be blunted due to hyperventilation, which is often associated with hypoxia.…”

Aging, Persistent Viral Infections, and Immunosenescence

“…3), which could elicit changes at the molecular level, leaving certain T-cell populations more susceptible to both intrinsic and extrinsic pathways of apoptosis after their egress from the blood. In humans, acute exercise also has been shown to activate caspase-8 and caspase-9 in blood lymphocytes without evidence of apoptosis, further indicating that lymphocytes that egress the blood during the recovery phase of exercise could be destined for subsequent apoptosis in the peripheral tissues (35). Changes in the surface expression of CD95 in blood lymphocytes after exercise have been reported, indicating that exercise might alter T-cell apoptosis susceptibility.…”