title: Hypoxic exercise training causes erythrocyte senescence and rheological dysfunction by depressed Gardos channel activity.
abstract: Despite enhancing cardiopulmonary and muscular fitness, the effect of hypoxic exercise training (HE) on hemorheological regulation remains unclear. This study investigates how HE modulates erythrocyte rheological properties and further explores the underlying mechanisms in the hemorheological alterations. Twenty-four sedentary males were randomly divided into hypoxic (HE; n = 12) and normoxic (NE; n = 12) exercise training groups. The subjects were trained on 60% of maximum work rate under 15% (HE) or 21% (NE) O(2) condition for 30 min daily, 5 days weekly for 5 wk. The results demonstrated that HE 1) downregulated CD47 and CD147 expressions on erythrocytes, 2) decreased actin and spectrin contents in erythrocytes, 3) reduced erythrocyte deformability under shear flow, and 4) diminished erythrocyte volume changed by hypotonic stress. Treatment of erythrocytes with H(2)O(2) that mimicked in vivo prooxidative status resulted in the cell shrinkage, rigidity, and phosphatidylserine exposure, whereas HE enhanced the eryptotic responses to H(2)O(2). However, HE decreased the degrees of clotrimazole to blunt ionomycin-induced shrinkage, rigidity, and cytoskeleton breakdown of erythrocytes, referred to as Gardos effects. Reduced erythrocyte deformability by H(2)O(2) was inversely related to the erythrocyte Gardos effect on the rheological function. Conversely, NE intervention did not significantly change resting and exercise erythrocyte rheological properties. Therefore, we conclude that HE rather than NE reduces erythrocyte deformability and volume regulation, accompanied by an increase in the eryptotic response to oxidative stress. Simultaneously, this intervention depresses Gardos channel-modulated erythrocyte rheological functions. Results of this study provide further insight into erythrocyte senescence induced by HE.
authors.affiliation: Graduate Institute of Physical Education, National Taiwan Sport University, Taiwan.
authors.forename: Tso-Yen
authors.initials: TY
authors.lastname: Mao
authors.forename: Li-Lan
authors.initials: LL
authors.lastname: Fu
authors.forename: Jong-Shyan
authors.initials: JS
authors.lastname: Wang
mesh_terms: D000328:Adult; D002452:Cell Count; D002469:Cell Separation; D004905:Erythrocyte Aging / Q000502:physiology*; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000378:metabolism / Q000502:physiology*; D004921:Erythropoietin / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000097:blood*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010809:Physical Fitness / Q000502:physiology*; D012156:Reticulocytes / Q000502:physiology; D012212:Rheology; D057185:Sedentary Behavior
chemical_list: D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D004921:Erythropoietin; D006861:Hydrogen Peroxide