Intermittent hypoxia has organ-specific effects on oxidative stress

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 295; no. 4; p. R1274
• Main Authors: Jun, Jonathan, Savransky, Vladimir, Nanayakkara, Ashika, Bevans, Shannon, Li, Jianguo, Smith, Philip L, Polotsky, Vsevolod Y
• Format: Journal Article
• Language: English
• Published: United States 01-10-2008
• Subjects: Acetophenones - pharmacology; Animals; Body Weight - physiology; Eating - physiology; Enzyme Inhibitors - pharmacology; Erythrocytes - metabolism; Glutathione - metabolism; Glutathione Disulfide - metabolism; Hypoxia - physiopathology; Lipid Peroxidation - drug effects; Lipoproteins, LDL - blood; Liver - drug effects; Liver - metabolism; Male; Malondialdehyde - blood; Malondialdehyde - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium - metabolism; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Phosphorylation - drug effects; Superoxide Dismutase - metabolism; Tyrosine - analogs & derivatives; Tyrosine - blood
• ISSN: 0363-6119
• DOI: 10.1152/ajpregu.90346.2008

Obstructive sleep apnea is characterized by upper airway collapse, leading to intermittent hypoxia (IH). It has been postulated that IH-induced oxidative stress may contribute to several chronic diseases associated with obstructive sleep apnea. We hypothesize that IH induces systemic oxidative stress by upregulating NADPH oxidase, a superoxide-generating enzyme. NADPH oxidase is regulated by a cytosolic p47(phox) subunit, which becomes phosphorylated during enzyme activation. Male C57BL/6J mice were exposed to IH with an inspired O(2) fraction nadir of 5% 60 times/h during the 12-h light phase (9 AM-9 PM) for 1 or 4 wk. In the aorta and heart, IH did not affect lipid peroxidation [malondialdehyde (MDA) level], nitrotyrosine level, or p47(phox) expression and phosphorylation. In contrast, in the liver, exposure to IH for 1 wk resulted in a trend to an increase in MDA levels, whereas IH for 4 wk resulted in a 38% increase in MDA levels accompanied by upregulation of p47(phox) expression and phosphorylation. Administration of an NADPH oxidase inhibitor, apocynin, during IH exposure attenuated IH-induced increases in hepatic MDA. In p47(phox)-deficient mice, MDA levels were higher at baseline and, unexpectedly, decreased during IH. In conclusion, oxidative stress levels and pathways under IH conditions are organ and duration specific.