Zhao K, An K, Fattaey H K, Johnson T C
Center for Basic Cancer Research, College of Arts and Sciences, Manhattan, Kansas, 66506, USA.
Exp Cell Res. 2000 Nov 1;260(2):181-8. doi: 10.1006/excr.2000.5008.
CeReS-18, a cell regulatory sialoglycopeptide, has been shown to inhibit proliferation of a wide array of target cells. In the present study, the effect of CeReS-18 on vascular smooth muscle cell (SMC) proliferation was characterized in cultured rat aorta SMCs (A7r5). More extensively, the effect of CeReS-18 on platelet-derived growth factor (PDGF)-induced SMC migration was examined using a modified Boyden's chamber assay. CeReS-18 inhibits both SMC proliferation and migration in a concentration-dependent, calcium-sensitive, and reversible manner. Furthermore, cells preincubated with the inhibitor had an increased sensitivity to CeReS-18-mediated inhibition of SMC migration. Immunoprecipitation and in vitro phosphorylation assays demonstrated that MAP kinase activity was inhibited in the CeReS-18-treated cells and pretreatment with CeReS-18 suppressed the activation of MAP kinase stimulated by PDGF. However, it is not likely that the suppression of the MAP kinase pathway was directly responsible for the ability of CeReS-18 to inhibit migration of the rat aorta smooth muscle cells since a MEK-specific inhibitor, PD98059, did not influence A7r5 cell migration.
CeReS-18是一种细胞调节性唾液酸糖肽，已被证明能抑制多种靶细胞的增殖。在本研究中，在培养的大鼠主动脉平滑肌细胞（A7r5）中对CeReS-18对血管平滑肌细胞（SMC）增殖的作用进行了表征。更广泛地，使用改良的博伊登室试验检测了CeReS-18对血小板衍生生长因子（PDGF）诱导的SMC迁移的作用。CeReS-18以浓度依赖性、钙敏感性和可逆性方式抑制SMC增殖和迁移。此外，用该抑制剂预孵育的细胞对CeReS-18介导的SMC迁移抑制具有更高的敏感性。免疫沉淀和体外磷酸化试验表明，在CeReS-18处理的细胞中MAP激酶活性受到抑制，并且用CeReS-18预处理可抑制由PDGF刺激的MAP激酶的激活。然而，MAP激酶途径的抑制不太可能直接导致CeReS-18抑制大鼠主动脉平滑肌细胞迁移的能力，因为MEK特异性抑制剂PD98059不影响A7r5细胞迁移。
