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前蛋白转化酶1和2(PC1和PC2)在神经分化的大鼠骨髓基质干细胞(BMSC)中表达。

Proprotein convertases 1 and 2 (PC1 and PC2) are expressed in neurally differentiated rat bone marrow stromal stem cells (BMSCs).

作者信息

Marandi Mohammad, Mowla Seyed Javad, Tavallaei Mahmoud, Yaghoobi Mohammad Mehdi, Jafarnejad Seyed Mehdi

机构信息

Department of Cellular and Molecular Biology, Imam Hossein University, Tehran, Iran.

出版信息

Neurosci Lett. 2007 Jun 15;420(3):198-203. doi: 10.1016/j.neulet.2007.04.041. Epub 2007 Apr 25.

Abstract

Neural-like cells derived from bone marrow stromal stem cells (BMSCs) have potential usefulness in cell therapy of degenerative or traumatic diseases of the central nervous system (CNS). The functional recovery mediated by these cells, however, depends on the secretion of neurotrophins (NTs) and their cognate receptors, as the main regulators of neural survival and death. The function of NTs is further modulated by proprotein convertase (PC) enzymes which function in converting proproteins (including proNTs) into their functional end products. Accordingly, failure in converting proprotein forms of NTs into their mature forms may lead to neuronal cell death. In the present study, we have investigated the expression profile of PCs before and during neural differentiation of rat BMSCs by RT-PCR. Our results show that major members of the PC family functioning in the constitutive secretory pathway (furin, PACE4 and PC7/LPC) are highly expressed in both undifferentiated and neurally differentiated BMSCs. In contrast, while PC1/PC3 and PC2 (specific to neural and endocrine cells) are absent in undifferentiated BMSCs, their expression is initiated upon the induction of differentiation. In conclusion, our results suggest that neurally differentiated BMSCs have acquired the functional machinery to process the precursor forms of proteins in both the constitutive and regulated pathways.

摘要

源自骨髓基质干细胞(BMSCs)的神经样细胞在中枢神经系统(CNS)退行性或创伤性疾病的细胞治疗中具有潜在用途。然而,这些细胞介导的功能恢复取决于神经营养因子(NTs)及其同源受体的分泌,它们是神经存活和死亡的主要调节因子。NTs的功能进一步受到前体蛋白转化酶(PC)的调节,PC可将前体蛋白(包括前体NTs)转化为其功能性终产物。因此,未能将NTs的前体蛋白形式转化为成熟形式可能导致神经元细胞死亡。在本研究中,我们通过逆转录聚合酶链反应(RT-PCR)研究了大鼠BMSCs神经分化之前和期间PC的表达谱。我们的结果表明,在组成型分泌途径中起作用的PC家族主要成员(弗林蛋白酶、PACE4和PC7/LPC)在未分化和神经分化的BMSCs中均高度表达。相比之下,虽然未分化的BMSCs中不存在PC1/PC3和PC2(特定于神经和内分泌细胞),但它们的表达在诱导分化时开始。总之,我们的结果表明,神经分化的BMSCs已经获得了在组成型和调节型途径中加工蛋白质前体形式的功能机制。

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