Intermittent hypoxia has organ-specific effects on oxidative stress
Intermittent hypoxia has organ-specific effects on oxidative stress
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DOI：
10.1152/ajpregu.90346.2008
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发表时间：
2008-10-01
影响因子：
2.8
通讯作者：
Polotsky, Vsevolod Y.
中科院分区：
文献类型：
--
作者：
Jun, Jonathan;Savransky, Vladimir;Polotsky, Vsevolod Y.
阻塞性睡眠呼吸暂停的特征是上呼吸道塌陷，导致间歇性缺氧（IH）。据推测，IH诱导的氧化应激可能导致与阻塞性睡眠呼吸暂停相关的几种慢性疾病。我们假设IH通过上调NADPH氧化酶（一种超氧化物生成酶）诱导全身氧化应激。NADPH氧化酶受胞质p47（phox）亚基调节，该亚基在酶活化过程中被磷酸化。雄性C57 BL/6 J小鼠在12小时光照期（上午9点至下午9点）暴露于吸入O2分数最低值为5%的IH 60次/h，持续1或4周。在主动脉和心脏，IH不影响脂质过氧化[丙二醛（MDA）水平]，硝基酪氨酸水平，或p47 phox的表达和磷酸化。相反，在肝脏中，暴露于IH 1周导致MDA水平增加的趋势，而IH 4周导致MDA水平增加38%，伴随着p47（phox）表达和磷酸化的上调。在IH暴露期间，给予NADPH氧化酶抑制剂夹竹桃苷可减弱IH诱导的肝MDA增加。在p47（phox）缺陷小鼠中，MDA水平在基线时较高，并且出乎意料地在IH期间降低。总之，IH条件下的氧化应激水平和途径是器官和持续时间特异性的。
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 p47phox 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.