N-acetyl-l-cysteine protects intestinal lymphocytes from apoptotic death after acute exercise in adrenalectomized mice.
Lymphocyte apoptosis has been observed after strenuous exercise. Both glucocorticoids (GC) and reactive oxygen species (ROS) have been suggested to contribute to exercise-induced lymphocyte apoptosis. The aims of this study were to 1) examine the direct contribution of GC during exercise-induced intestinal lymphocyte (IL) apoptosis and 2) determine the contribution of oxidative stress, in the absence of GC, to exercise-induced IL apoptosis. Mice were bilaterally adrenalectomized (ADX) and randomly assigned to receive saline (SAL) or N-acetyl-l-cysteine (NAC) 30 min before treadmill exercise (EX). EX consisted of 90 min of continuous running at a 2 degrees slope (30 min at 22 m/min, 30 min at 25 m/min; and 30 min at 28 m/min), and then killed immediately (Imm) or 24 h (24 h) postexercise. Control mice were exposed to a nonexercised (NonEX) condition consisting of treadmill noise and vibration without running. ILs were isolated and measured for apoptotic (phosphatidylserine externalization, mitochondrial membrane depolarization, Bcl-2, caspase 3, and cytosolic cytochrome c) and oxidative stress (H(2)O(2) and glutathione) markers. Plasma was analyzed for corticosterone (CORT) by radioimmunoassay. ADX eliminated the exercise-induced elevation in CORT but did not prevent IL apoptosis and cell loss relative to NonEX mice. In contrast, administration of NAC to ADX mice protected ILs from apoptotic cell death and inhibited post-exercise cell loss. These findings suggest that GC are not responsible for exercise-induced apoptosis and cell loss of ILs. The protective effect provided by the antioxidant NAC strongly suggest that oxidative stress is the primary pathway for IL apoptosis and cell loss after strenuous exercise.
Quadrilatero
Joe
J
Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
Hoffman-Goetz
Laurie
L
D000111:Acetylcysteine / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007422:Intestines / Q000166:cytology*; D008214:Lymphocytes / Q000187:drug effects*; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology*; D011419:Propidium / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D000954:Antigens, Surface; D016166:Free Radical Scavengers; D005938:Glucocorticoids; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D011419:Propidium; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D003345:Corticosterone; D000111:Acetylcysteine