Intermittent hypoxia has organ-specific effects on oxidative stress.

نویسندگان

  • Jonathan Jun
  • Vladimir Savransky
  • Ashika Nanayakkara
  • Shannon Bevans
  • Jianguo Li
  • Philip L Smith
  • Vsevolod Y Polotsky
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Tempol relieves lung injury in a rat model of chronic intermittent hypoxia via suppression of inflammation and oxidative stress

Objective(s): Obstructive sleep apnea (OSA) is confirmed to cause lesions in multiple organs, especially in the lung tissue. Tempol is an antioxidant that has been reported to restrain inflammation and oxidative stress, with its role in OSA-induced lung injury being unclear. This study aimed to investigate the beneficial effect of tempol on chronic intermittent hypoxia (IH)-induced lung injury....

متن کامل

11 Farias.indd

Melatonin (N-acetyl-5-methoxytryptamine) is the main secretory product of the pineal gland in all mammals including humans, but it is also produced in other organs. It has been previously demonstrated to be a powerful organ-protective substance under oxidative stress conditions. The aim of this study was to evaluate the protective effect of melatonin in several organs such as heart, lung, kidne...

متن کامل

Intermittent Hypoxia Can Aggravate Motor Neuronal Loss and Cognitive Dysfunction in ALS Mice

BACKGROUND Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chr...

متن کامل

Sleep apnea awakens cancer

Obstructive sleep apnea syndrome (OSA) is a highly prevalent disorder affecting approximately 4 to 10% of adults that has been implicated in a large spectrum of end-organ morbidities. OSA is characterized by repetitive obstructions of the upper airway during sleep that result in intermittent hypoxia (IH), increased inspiratory efforts, and ultimately sleep fragmentation (SF). A large body of re...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • American journal of physiology. Regulatory, integrative and comparative physiology

دوره 295 4  شماره 

صفحات  -

تاریخ انتشار 2008