Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy.
PLoS One. 2010 Jan 13;5(1):e8670. doi: 10.1371/journal.pone.0008670.
Like other steroid hormones, vitamin D elicits both transcriptional events and rapid non genomic effects. Vitamin D receptor (VDR) localization and mechanisms of VDR-triggered non genomic responses are still controversial. Although anticoagulant effects of vitamin D have been reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we characterized the expression and cellular localization of VDR in human platelets and in a megakaryocyte lineage. Human platelets and their TPA-differentiated precursors expressed a classical 50 kDa VDR protein, which increased with megakaryocytes maturation. By biochemical fractionation studies we demonstrated the presence of the receptor in the soluble and mitochondrial compartment of human platelets, and the observation was confirmed by immunoelectron microscopy analysis. Similar localization was found in mature megakaryocytes, where besides its classical nuclear localization the receptor was evident as soluble and mitochondria resident protein.
The results reported here suggest that megakaryocytopoiesis and platelet activation, which are calcium-dependent events, might be modulated by a mitochondrial non genomic activity of VDR. These data open challenging future studies on VDR physiological role in platelets and more generally in mitochondria.
与其他甾体激素一样，维生素 D 既能引发转录事件，也能引发快速非基因组效应。维生素 D 受体 (VDR) 的定位以及 VDR 引发的非基因组反应的机制仍存在争议。尽管已经报道了维生素 D 的抗凝作用，并且在单核细胞和血管细胞中已经对 VDR 信号转导进行了描述，但对于人类血小板中的 VDR 表达和功能（已知是其他甾体的靶标）却一无所知。
方法/主要发现：在这项研究中，我们研究了 VDR 在人类血小板和巨核细胞系中的表达和细胞定位。人类血小板及其 TPA 分化的前体表达一种经典的 50 kDa VDR 蛋白，该蛋白随着巨核细胞的成熟而增加。通过生化分级分离研究，我们证明了受体存在于人类血小板的可溶性和线粒体部分，免疫电镜分析也证实了这一观察结果。在成熟的巨核细胞中也发现了类似的定位，除了经典的核定位外，受体还作为可溶性和线粒体驻留蛋白存在。
这里报道的结果表明，巨核细胞生成和血小板激活是钙依赖性事件，可能受到 VDR 的线粒体非基因组活性的调节。这些数据为未来研究 VDR 在血小板中的生理作用以及更普遍的线粒体中的作用开辟了新的挑战。
