异牛肝菌素通过阻断SM22α泛素化降解抑制血管平滑肌细胞表型转化
发布时间：2019-05-16 12:14
【摘要】：从黄乳粘盖牛肝菌(Suillus flavus)中分离得到的异牛肝菌素(iso-suillin)具有显著的抗肿瘤活性,但其在心血管系统的功效尚不明确。本研究用不同浓度的异牛肝菌素预处理原代血管平滑肌细胞(vascular smooth muscle cell,VSMC)24 h或48 h后,再采用血小板源性生长因子(platelet-derived growth factor,PDGF)-BB处理细胞,细胞计数法检测VSMC增殖活性;流式细胞术检测细胞周期分布;Western blot分析检测蛋白表达情况;免疫沉淀检测平滑肌22 alpha(smooth muscle 22 alpha,SM22α)磷酸化和泛素化水平。结果显示,异牛肝菌素显著抑制PDGF-BB引发的VSMC增殖;上调分化标志蛋白SM22α表达,下调增殖相关蛋白PCNA表达;抑制SM22α磷酸化及其泛素化降解,且该过程可能与其阻断蛋白激酶C(protein kinase C,PKC)δ的活性有关。通过以上结果推测,异牛肝菌素通过抑制PKCδ的活性,降低SM22α磷酸化水平,阻止SM22α泛素化降解,进而抑制VSMC表型转化,发挥血管保护的功能。
[Abstract]:Isoborubicin (iso-suillin) isolated from (Suillus flavus) has significant antitumor activity, but its effect on cardiovascular system is not clear. In this study, primary vascular smooth muscle cells (vascular smooth muscle cell,VSMC) were pretreated with different concentrations of isoborubicin for 24 h or 48 h, and then treated with platelet-derived growth factor (platelet-derived growth factor,PDGF)-BB. The proliferation activity of VSMC was detected by cell counting. Cell cycle distribution was detected by flow cytometry, protein expression was detected by; Western blot analysis, and phosphorylation and ubiquitin levels of smooth muscle 22 alpha (smooth muscle 22 alpha,SM22 伪 were detected by immunoprecipitation. The results showed that genistein significantly inhibited the proliferation of VSMC induced by PDGF-BB, upregulated the expression of differentiation marker protein SM22 伪 and down-regulated the expression of proliferation-related protein PCNA. Inhibition of SM22 伪 phosphorylation and ubiquitin degradation may be related to its blocking the activity of protein kinase C (protein kinase C, PKC) 未. Through the above results, it is speculated that isoborubicin can inhibit the activity of PKC 未, decrease the phosphorylation level of SM22 伪, prevent the degradation of SM22 伪 ubiquitin, and then inhibit the phenotypic transformation of VSMC and play the role of vascular protection.
【作者单位】： 河北医科大学基础医学院;河北省食品检验研究院河北省食品安全重点实验室;北京食品科学研究院中国肉类食品综合研究中心;
【基金】：“十三五”国家重点研发计划重点专项(2016YFF0202300) 科技部质检行业公益专项(201510208-08) 国家自然科学基金青年科学基金项目(81300225) 河北省自然科学基金资助项目(H2015206467) 河北省高等学校优秀青年基金项目(YQ2013018)
【分类号】：R151
本文编号：2478269
[Abstract]:Isoborubicin (iso-suillin) isolated from (Suillus flavus) has significant antitumor activity, but its effect on cardiovascular system is not clear. In this study, primary vascular smooth muscle cells (vascular smooth muscle cell,VSMC) were pretreated with different concentrations of isoborubicin for 24 h or 48 h, and then treated with platelet-derived growth factor (platelet-derived growth factor,PDGF)-BB. The proliferation activity of VSMC was detected by cell counting. Cell cycle distribution was detected by flow cytometry, protein expression was detected by; Western blot analysis, and phosphorylation and ubiquitin levels of smooth muscle 22 alpha (smooth muscle 22 alpha,SM22 伪 were detected by immunoprecipitation. The results showed that genistein significantly inhibited the proliferation of VSMC induced by PDGF-BB, upregulated the expression of differentiation marker protein SM22 伪 and down-regulated the expression of proliferation-related protein PCNA. Inhibition of SM22 伪 phosphorylation and ubiquitin degradation may be related to its blocking the activity of protein kinase C (protein kinase C, PKC) 未. Through the above results, it is speculated that isoborubicin can inhibit the activity of PKC 未, decrease the phosphorylation level of SM22 伪, prevent the degradation of SM22 伪 ubiquitin, and then inhibit the phenotypic transformation of VSMC and play the role of vascular protection.
【作者单位】： 河北医科大学基础医学院;河北省食品检验研究院河北省食品安全重点实验室;北京食品科学研究院中国肉类食品综合研究中心;
【基金】：“十三五”国家重点研发计划重点专项(2016YFF0202300) 科技部质检行业公益专项(201510208-08) 国家自然科学基金青年科学基金项目(81300225) 河北省自然科学基金资助项目(H2015206467) 河北省高等学校优秀青年基金项目(YQ2013018)
【分类号】：R151
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