Kramerov A A, Saghizadeh M, Caballero S, Shaw L C, Li Calzi S, Bretner M, Montenarh M, Pinna L A, Grant M B, Ljubimov A V
Ophthalmology Research Laboratories, Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Davis-2025, Los Angeles, CA 90048, USA.
Mol Cell Biochem. 2008 Sep;316(1-2):177-86. doi: 10.1007/s11010-008-9831-4. Epub 2008 Jul 9.
Ubiquitous protein kinase CK2 participates in a variety of key cellular functions. We have explored CK2 involvement in angiogenesis. As shown previously, CK2 inhibition reduced endothelial cell proliferation, survival and migration, tube formation, and secondary sprouting on Matrigel. Intraperitoneally administered CK2 inhibitors significantly reduced preretinal neovascularization in a mouse model of proliferative retinopathy. In this model, CK2 inhibitors had an additive effect with somatostatin analog, octreotide, resulting in marked dose reduction for the drug to achieve the same effect. CK2 inhibitors may thus emerge as potent future drugs aimed at inhibiting pathological angiogenesis. Immunostaining of the retina revealed predominant CK2 expression in astrocytes. In human diabetic retinas, mRNA levels of all CK2 subunits decreased, consistent with increased apoptosis. Importantly, a specific CK2 inhibitor prevented recruitment of bone marrow-derived hematopoietic stem cells to areas of retinal neovascularization. This may provide a novel mechanism of action of CK2 inhibitors on newly forming vessels.
普遍存在的蛋白激酶CK2参与多种关键的细胞功能。我们已经探究了CK2在血管生成中的作用。如先前所示，抑制CK2可降低内皮细胞的增殖、存活和迁移、管腔形成以及在基质胶上的二次出芽。腹腔注射CK2抑制剂可显著减少增殖性视网膜病变小鼠模型中的视网膜前新生血管形成。在该模型中，CK2抑制剂与生长抑素类似物奥曲肽具有相加作用，从而使药物达到相同效果所需的剂量显著降低。因此，CK2抑制剂可能会成为未来旨在抑制病理性血管生成的有效药物。视网膜免疫染色显示星形胶质细胞中CK2表达占主导。在人类糖尿病视网膜中，所有CK2亚基的mRNA水平均下降，这与细胞凋亡增加一致。重要的是，一种特异性CK2抑制剂可阻止骨髓来源的造血干细胞募集至视网膜新生血管区域。这可能为CK2抑制剂对新形成血管的作用提供一种新的作用机制。
