Translational Neuroscience, Institute of Medical Sciences, School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom.
Glia. 2012 Dec;60(12):1964-76. doi: 10.1002/glia.22412. Epub 2012 Aug 28.
Retinaldehyde dehydrogenases (RALDH) catalyze the synthesis of the regulatory factor retinoic acid (RA). Cultured astrocytes express several of the RALDH enzyme family, and it has been assumed that this can be extrapolated to astrocytes in vivo. However, this study finds that few astrocytes in the rodent brain express detectable RALDH enzymes, and only when these cells are grown in culture are these enzymes upregulated. Factors controlling the expression of the RALDHs in cultured astrocytes were explored to determine possible reasons for differences between in vitro versus in vivo expression. Retinoids were found to feedback to suppress several of the RALDHs, and physiological levels of retinoids may be one route by which astrocytic RALDHs are maintained at low levels. In the case of RALDH2, in vivo reduction of vitamin A levels in rats resulted in an increase in astrocyte RALDH2 expression in the hippocampus. Other factors though are likely to control RALDH expression. A shift in astrocytic RALDH subcellular localization is a potential mechanism for regulating RA signaling. Under conditions of vitamin A deficiency, RALDH2 protein moved from the cytoplasm to the nucleus where it may synthesize RA at the site of the nuclear RA receptors. Similarly, in conditions of oxidative stress RALDH1 and RALDH2 moved from the cytoplasm to a predominantly nuclear position. Thus, the RALDHs have been revealed to be dynamic in their expression in astrocytes where they may maintain retinoid homeostasis in the brain.
视黄醛脱氢酶（RALDH）催化调节因子视黄酸（RA）的合成。培养的星形胶质细胞表达几种 RALDH 酶家族，并且假定这可以外推到体内的星形胶质细胞。然而，这项研究发现，啮齿动物大脑中的少数星形胶质细胞表达可检测到的 RALDH 酶，并且只有当这些细胞在培养中生长时，这些酶才会被上调。为了确定体外与体内表达之间差异的可能原因，研究了控制培养星形胶质细胞中 RALDH 表达的因素。发现类视黄醇可以反馈抑制几种 RALDH，并且生理水平的类视黄醇可能是维持星形胶质细胞 RALDH 低水平的一种途径。在 RALDH2 的情况下，体内降低大鼠的维生素 A 水平导致海马体中星形胶质细胞 RALDH2 表达增加。不过，其他因素可能控制 RALDH 的表达。星形胶质细胞 RALDH 亚细胞定位的转变是调节 RA 信号的潜在机制。在维生素 A 缺乏的情况下，RALDH2 蛋白从细胞质转移到细胞核，在那里它可能在核 RA 受体部位合成 RA。同样，在氧化应激条件下，RALDH1 和 RALDH2 从细胞质转移到主要的核位置。因此，RALDH 在星形胶质细胞中的表达是动态的，它们可能在大脑中维持类视黄醇的稳态。
