Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Mol Sci. 2019 Jul 24;20(15):3610. doi: 10.3390/ijms20153610.
All- retinoic acid (AtRA), an active metabolite of vitamin A, is recognized for its classical action as an endocrine hormone that triggers genomic effects mediated through nuclear receptors RA receptors (RARs). New evidence shows that atRA-mediated cellular responses are biphasic with rapid and delayed responses. Most of these rapid atRA responses are the outcome of its binding to cellular retinoic acid binding protein 1 (CRABP1) that is predominantly localized in cytoplasm and binds to atRA with a high affinity. This review summarizes the most recent studies of such non-genomic outcomes of atRA and the role of CRABP1 in mediating such rapid effects in different cell types. In embryonic stem cells (ESCs), atRA-CRABP1 dampens growth factor sensitivity and stemness. In a hippocampal neural stem cell (NSC) population, atRA-CRABP1 negatively modulates NSC proliferation and affects learning and memory. In cardiomyocytes, atRA-CRABP1 prevents over-activation of calcium-calmodulin-dependent protein kinase II (CaMKII), protecting heart function. These are supported by the fact that gene knockout (KO) mice exhibit multiple phenotypes including hippocampal NSC expansion and spontaneous cardiac hypertrophy. This indicates that more potential processes/signaling pathways involving atRA-CRABP1 may exist, which remain to be identified.
全反式视黄酸（AtRA），维生素 A 的一种活性代谢物，作为一种内分泌激素，通过核受体视黄酸受体（RARs）介导基因组效应而被广泛认知。新的证据表明，AtRA 介导的细胞反应具有双相性，包括快速和延迟反应。这些快速的 AtRA 反应大多是由于它与细胞视黄酸结合蛋白 1（CRABP1）结合的结果，CRABP1 主要位于细胞质中，与 AtRA 具有高亲和力。这篇综述总结了最近关于 AtRA 的非基因组作用以及 CRABP1 在不同细胞类型中介导这种快速作用的研究。在胚胎干细胞（ESCs）中，AtRA-CRABP1 降低了生长因子的敏感性和干细胞特性。在海马神经干细胞（NSC）群体中，AtRA-CRABP1 负调控 NSC 的增殖，并影响学习和记忆。在心肌细胞中，AtRA-CRABP1 可防止钙调蛋白依赖性蛋白激酶 II（CaMKII）过度激活，从而保护心脏功能。基因敲除（KO）小鼠表现出多种表型，包括海马 NSC 扩增和自发性心肌肥厚，这一事实为上述结论提供了支持。这表明可能存在更多涉及 AtRA-CRABP1 的潜在过程/信号通路，这些通路仍有待确定。
