• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Potent and selective inhibition of matrix metalloproteinases by lanthanide trichloride
【24h】

Potent and selective inhibition of matrix metalloproteinases by lanthanide trichloride

机译：三氯化镧有效和选择性抑制基质金属蛋白酶

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Matrix metalloproteinases (MMPs) are a family of Zn-containing and Ca-dependent proteases with vital roles in extracellular matrix remodeling. Deregulation of MMPs occurs in many pathological conditions such as cardiovascular diseases, inflammation, and cancer. The therapeutic potential of MMP inhibitors has been demonstrated in diseases such as arthritis and cancer. Here we demonstrated that the 3-valent lanthanide compounds LaCl _(3) , TbCl _(3) , GdCl _(3) , YbCl _(3) , and EuCl _(3) inhibit MMPs such as MMP-2, MMP-13, and MMP-14 (MT1-MMP). The inhibition is more potent and selective toward MT1-MMP compared to the other MMPs. EuCl _(3) was further selected to study the enzyme kinetics of the MT1-MMP inhibition. The results showed that the inhibition is a mixed type with anti-competition and non-competitive types, which indicated that inhibition was achieved by the compound bound to the non-active center of MT1-MMP and changing the enzyme conformation. The interaction between EuCl _(3) and MT1-MMP was further studied by UV-visible (UV-vis) light absorption. EuCl _(3) caused a slight blue shift of the maximum absorption wavelength of MT1-MMP, indicating the interaction reduced protein hydrophobicity. Moreover, EuCl _(3) exerted substantial inhibitory effects on the migration of HT-1080 cells. Thus, EuCl _(3) may play a role in modulating tumor cell behavior by inhibiting MMPs activities especially the MT1-MMP activity. These findings provide initial insight into the biological activity and potential therapeutic value of EuCl _(3) .
机译：基质金属蛋白酶（MMP）是一类含锌和钙依赖性蛋白酶，在细胞外基质重塑中起着至关重要的作用。 MMP的失调发生在许多病理状况下，例如心血管疾病，炎症和癌症。 MMP抑制剂的治疗潜力已在诸如关节炎和癌症的疾病中得到证明。在这里，我们证明了三价镧系元素LaCl _（3），TbCl _（3），GdCl _（3），YbCl _（3）和EuCl _（3）会抑制MMP，例如MMP-2，MMP- 13和MMP-14（MT1-MMP）。与其他MMP相比，抑制作用更强，对MT1-MMP更具选择性。进一步选择EuCl_（3）来研究MT1-MMP抑制的酶动力学。结果表明，该抑制作用是具有反竞争和非竞争作用的混合类型，表明该抑制作用是通过与MT1-MMP非活性中心结合的化合物改变酶构象而实现的。 EuCl_（3）与MT1-MMP之间的相互作用通过紫外-可见光（UV-vis）吸收进一步研究。 EuCl_（3）引起MT1-MMP最大吸收波长的轻微蓝移，表明相互作用降低了蛋白的疏水性。此外，EuCl_（3）对HT-1080细胞的迁移发挥了实质性的抑制作用。因此，EuCl_（3）可能通过抑制MMPs活性，特别是MT1-MMP活性，在调节肿瘤细胞行为中发挥作用。这些发现为EuCl_（3）的生物学活性和潜在的治疗价值提供了初步的见识。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号