Effects of chronic continuous hypoxia on the expression of SLC4A8 (NDCBE) in neonatal versus adult mouse brain.

Effects of chronic continuous hypoxia on the expression of SLC4A8 (NDCBE) in neonatal versus adult mouse brain.
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DOI:
10.1016/j.brainres.2008.08.033
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发表时间:
2008-10-31
期刊:
影响因子:
2.9
通讯作者:
Boron WF
Boron WF
中科院分区:
医学3区
文献类型:
--
作者:
Chen LM;Haddad GG;Boron WF

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钠偶联HCO 3转运体(NCBTs)在脑pH调节中起重要作用。一种NCBT,Na驱动的Cl-HCO 3交换器(SLC 4A 8或NDCBE),似乎是细胞内pH(pHi)的主要调节器,至少在一些海马锥体神经元中是如此。NDCBE在啮齿动物脑中的整个中枢神经系统中广泛表达。在先前的研究中,已经证明CCH降低了小鼠大脑四个区域中NBCn 1和NBCn 2蛋白的丰度:大脑皮层(CX),皮层下(SCX),小脑(CB)和海马(HC)。本文报道了CCH(11%O2)对小鼠脑NDCBE蛋白表达的影响。新生小鼠(从P2开始)或成年小鼠(从P90开始)接受常氧或CCH,持续时间为14或28天。膜蛋白水平进行了评估,使用我们的多克隆抗体针对NDCBE蛋白质印迹。在新生儿中,CCH显着降低NDCBE表达HC后14天和SCX后28天,但没有显着影响的其他组合的区域/持续时间。然而,在成年人中,CCH显著降低(20-50%)NDCBE在所有四个脑区的表达,无论是14天和28天的持续时间。因此,小鼠大脑表现出显着的NDCBE蛋白表达CCH的反应发育差异。我们推测,成年NDCBE蛋白水平的下降,这可能是不成比例的其他蛋白质的减少,可能是一种适应性反应,减少能量消耗和/或稳定大脑pH值的一部分。幼年动物的较小或无反应可能与新生儿缺氧耐受有关。
Na-coupled HCO3 transporters (NCBTs) play important roles in brain pH regulation. One NCBT, the Na-driven Cl-HCO3 exchanger (SLC4A8 or NDCBE), appears to be the major regulator of intracellular pH (pHi), at least in some hippocampal pyramidal neurons. NDCBE is widely expressed throughout the central nervous system in rodent brain. In a previous study, it has been demonstrated that CCH decreases the abundance of NBCn1 and NBCn2 proteins in four regions of the mouse brain: cerebral cortex (CX), subcortex (SCX), cerebellum (CB), and hippocampus (HC). Here we report the effect of CCH (11% O2) on the expression of NDCBE protein in mouse brain. Neonates (beginning at age P2) or adult mice (beginning at P90) were subjected to either normoxia or CCH for durations of 14 or 28 days. Membrane-protein levels were assessed by western blotting using our polyclonal antibody directed against NDCBE. In neonates, CCH significantly decreased NDCBE expression in HC after 14 days and SCX after 28 days, but had no significant effect for other combinations of region/duration. In adults, however, CCH significantly decreased (by 20–50%) the expression of NDCBE in all four brain regions, both with 14 and 28 days’ duration. Thus, the mouse brain exhibits marked developmental differences in the response of NDCBE protein expression to CCH. We hypothesize that decreases in adult NDCBE protein levels, which are probably out of proportion to the decreases in other proteins, may be part of an adaptive response that reduces energy consumption and/or stabilizes brain pHi. The smaller or absent responses in the young animals could be related to neonatal hypoxia tolerance.
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