Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha.

Regulation of skin microvasculature angiogenesis, cell migration, and permeability by a specific inhibitor of PKCalpha.
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通过 PKCα 的特异性抑制剂调节皮肤微血管血管生成、细胞迁移和渗透性。

DOI:
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发表时间:
2006
影响因子:
6.5
通讯作者:
V. Chaudhuri
V. Chaudhuri
中科院分区:
医学1区
文献类型:
--
作者:
S. Bokhari;Lisa Zhou;M. Karasek;Sarita G Paturi;V. Chaudhuri

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蛋白激酶C (PKC)的激活诱导微血管内皮细胞形态的表型变化,影响微血管的主要功能。这些功能包括血管生成中萌芽的最初阶段,受伤后的细胞迁移和血管通透性。导致这些变化的PKC的特定同工异构体以前没有被确定。在这项研究中,我们使用两种炎症剂,il -1 β和phorbol myristic acetate,来激活PKC同工酶和PKCalpha (Gö6976)和PKCbeta (hispidin)的特异性抑制剂,以区分这些异构体如何控制血管生成、伤口愈合和通透性。在所有情况下,与pkcβ的抑制相比,只有PKCalpha的抑制抑制了这些功能。另外,Gö6976 (RT-PCR、Western blots和免疫组化)对细胞膜和细胞质中PKCalpha磷酸化和非磷酸化形式的变化的作用机制分析证实了Gö6976对PKCalpha抑制的特异性。因此,这些研究表明PKCalpha亚型在三种主要内皮细胞功能中具有特异性和调节作用,这些功能在维持微血管稳态中很重要。
Activation of protein kinase C (PKC) induces phenotypic changes in the morphology of microvascular endothelial cells that affect major functions of the microvasculature. These functions include the first stages of sprouting in angiogenesis, cell migration following wounding, and vascular permeability. The specific isoform(s) of PKC responsible for each of these changes has not been previously identified. In this study, we used two inflammatory agents, IL-1beta and phorbol myristic acetate, to activate PKC isozymes and specific inhibitors of PKCalpha (Gö6976) and PKCbeta (hispidin) to distinguish how each of these isoform(s) controls angiogenesis, wound healing, and permeability. In all cases, only inhibition of PKCalpha inhibited each of these functions when compared to the inhibition of PKCbeta. Additional analysis of the mechanism of action of Gö6976 (RT-PCR, Western blots, and immunohistochemistry) of the changes in the phosphorylated and nonphosphorylated forms of PKCalpha in the cell membrane and cytoplasm confirmed the specificity of PKCalpha inhibition by Gö6976. These studies therefore indicate a specific and a regulatory role of the PKCalpha isoform in three major endothelial cell functions that are important in the maintenance of microvascular homeostasis.
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