Differential regulation of the ascorbic acid transporter SVCT2 during development and in response to ascorbic acid depletion.

Differential regulation of the ascorbic acid transporter SVCT2 during development and in response to ascorbic acid depletion.
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DOI:
10.1016/j.bbrc.2011.09.146
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发表时间:
2011-11-04
影响因子:
3.1
通讯作者:
May, James M.
May, James M.
中科院分区:
生物学4区
文献类型:
--
作者:
Meredith, M. Elizabeth;Harrison, Fiona E.;May, James M.

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钠依赖性维生素C转运蛋白2(SVCT 2)是唯一在脑中显著表达的抗坏血酸(ASC)转运蛋白。它是生命所必需的,在大脑发育过程中至关重要,以提供足够的ASC水平。为了评估SVCT 2在发育中的大脑中的功能,我们研究了小鼠大脑中SVCT 2 mRNA和蛋白质的时间依赖性表达,使用肝脏作为比较组织,因为它是ASC合成的部位。我们发现SVCT 2的表达与发育中大脑中的ASC水平呈反比关系。在皮质和小脑,ASC水平在整个胚胎晚期和出生后早期阶段高,并随着年龄的增长而下降,而SVCT 2 mRNA和蛋白水平在胚胎中低,并随着年龄的增长而增加。肝脏观察到不同的反应,其中ASC水平和SVCT 2表达在整个胚胎发生过程中都很低,并且在出生后增加。为了确定低细胞内ASC是否能够驱动SVCT 2表达,我们在不能合成ASC的成年小鼠中通过饮食耗尽ASC。我们观察到,SVCT 2 mRNA和蛋白不受大脑皮层ASC耗竭的影响,但SVCT 2蛋白表达增加,在小脑和肝脏ASC耗竭。结果表明,SVCT 2的表达在胚胎发育和成年期受到不同的调节。
The sodium-dependent vitamin C transporter-2 (SVCT2) is the only ascorbic acid (ASC) transporter significantly expressed in brain. It is required for life and critical during brain development to supply adequate levels of ASC. To assess SVCT2 function in the developing brain, we studied time-dependent SVCT2 mRNA and protein expression in mouse brain, using liver as a comparison tissue because it is the site of ASC synthesis. We found that SVCT2 expression followed an inverse relationship with ASC levels in the developing brain. In cortex and cerebellum, ASC levels were high throughout late embryonic stages and early post-natal stages and decreased with age, whereas SVCT2 mRNA and protein levels were low in embryos and increased with age. A different response was observed for liver, in which ASC levels and SVCT2 expression were both low throughout embryogenesis and increased post-natally. To determine whether low intracellular ASC might be capable of driving SVCT2 expression, we depleted ASC by diet in adult mice unable to synthesize ASC. We observed that SVCT2 mRNA and protein were not affected by ASC depletion in brain cortex, but SVCT2 protein expression was increased by ASC depletion in the cerebellum and liver. The results suggest that expression of the SVCT2 is differentially regulated during embryonic development and in adulthood.
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