Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain
Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain
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DOI：
10.1152/ajpregu.00497.2007
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发表时间：
2007-12-01
影响因子：
2.8
通讯作者：
Boron, Walter F.
中科院分区：
文献类型：
--
作者：
Chen, Li-Ming;Choi, Inyeong;Boron, Walter F.
在哺乳动物的中枢神经系统中，缺氧会引起广泛的生理影响，这些影响往往取决于发育阶段。影响之一是pH内平衡的改变。Na +偶联HCO3-转运体在细胞内pH调节中发挥关键作用，其中NCBE和NBCn1等转运体在中枢神经系统中大量表达。在本研究中，我们研究了慢性持续缺氧对小鼠大脑中两种电中性Na偶联HCO3-转运体SLC4a7 （NBCn1）和SLC4a10 （NCBE）表达的影响，这是首次对酸碱转运体进行此类研究。我们将小鼠置于常压室中，从出生后2天（P2）或P90开始，维持常氧（21%吸入O-2）或持续慢性缺氧（11%吸入O-2），持续14天或28天。我们通过Western blot分析评估蛋白质丰度，在每种情况下加载等量的总蛋白。在大多数情况下，缺氧在14天和28天后，幼鼠和成年鼠的大脑皮层、皮层下、小脑和海马中的NBCn1水平降低了20- 50%，NCBE水平降低了15-40%。我们假设，这些与预期的脑蛋白水平总体下降不成比例的减少，可能对减少能量消耗特别重要。
In the mammalian CNS, hypoxia causes a wide range of physiological effects, and these effects often depend on the stage of development. Among the effects are alterations in pH homeostasis. Na + -coupled HCO3- transporters can play critical roles in intracellular pH regulation and several, such as NCBE and NBCn1, are expressed abundantly in the central nervous system. In the present study, we examined the effect of chronic continuous hypoxia on the expression of two electroneutral Na- coupled HCO3- transporters, SLC4a7 (NBCn1) and SLC4a10 (NCBE), in mouse brain, the first such study on any acid-base transporter. We placed the mice in normobaric chambers and either maintained normoxia (21% inspired O-2) or imposed continuous chronic hypoxia (11% O-2) for a duration of either 14 days or 28 days, starting from ages of either postnatal age 2 days (P2) or P90. We assessed protein abundance by Western blot analysis, loading equal amounts of total protein for each condition. In most cases, hypoxia reduced NBCn1 levels by 20- 50%, and NCBE levels by 15-40% in cerebral cortex, subcortex, cerebellum, and hippocampus, both after 14 and 28 days, and in both pups and adults. We hypothesize that these decreases, which are out of proportion to the expected overall decreases in brain protein levels, may especially be important for reducing energy consumption.