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血根碱抑制血管内皮生长因子诱导的Akt磷酸化。

Sanguinarine inhibits VEGF-induced Akt phosphorylation.

作者信息

Basini Giuseppina, Santini Sujen Eleonora, Bussolati Simona, Grasselli Francesca

机构信息

Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti, Sezione di Fisiologia, Facolta di Medicina Veterinaria, Via del Taglio 8, 43100 Parma, Italy.

出版信息

Ann N Y Acad Sci. 2007 Jan;1095:371-6. doi: 10.1196/annals.1397.040.

DOI:10.1196/annals.1397.040
PMID:17404049
Abstract

Angiogenesis is the process of vascular growth by sprouting of preexisting vessels. This process impacts significantly on many important disease states including cancer, diabetic retinopathy, and arthritis. Endothelial cells receive multiple information from their environment, which leads them to progress along all stages of new vessel formation. Vascular endothelial growth factor (VEGF), in particular appears to be a master regulator of this process. This molecule interacts with cellular receptors and communicates with cell nucleus through a network of intracellular signaling, most of all by activating Akt pathway. This activation accounts for many of VEGF effects, including cell survival, migration, tube formation, and promotion of NO release. Sanguinarine (SA), an alkaloid isolated from Sanguinaria canadensis, is known for its antiangiogenetic effects by suppressing basal and VEGF-induced new vessel growth. This article was aimed to evaluate the possible effect of SA (300 nM) on Akt phosphorylation in a porcine aortic endothelial cell line. The alkaloid significantly (P < 0.001) inhibited the VEGF-induced Akt increase, thus suggesting that this mode of action could be responsible, at least partially, for the antiangiogenetic effect of SA.

摘要

血管生成是通过已有血管发芽实现血管生长的过程。这一过程对包括癌症、糖尿病视网膜病变和关节炎在内的许多重要疾病状态都有显著影响。内皮细胞从其周围环境接收多种信息,这些信息引导它们经历新血管形成的各个阶段。特别是血管内皮生长因子(VEGF)似乎是这一过程的主要调节因子。该分子与细胞受体相互作用,并通过细胞内信号网络与细胞核进行通信,其中最重要的是通过激活Akt通路。这种激活解释了VEGF的许多作用,包括细胞存活、迁移、管腔形成以及促进一氧化氮释放。血根碱(SA)是从加拿大血根草中分离出的一种生物碱,以其通过抑制基础和VEGF诱导的新血管生长的抗血管生成作用而闻名。本文旨在评估SA(300 nM)对猪主动脉内皮细胞系中Akt磷酸化的可能影响。该生物碱显著(P < 0.001)抑制了VEGF诱导的Akt增加,因此表明这种作用模式可能至少部分地是SA抗血管生成作用的原因。

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