Plasminogen K5 activates mitochondrial apoptosis pathway in endothelial cells by regulating Bak and Bcl-xL subcellular distribution

Xiaoqiong Gu, Yachao Yao, Rui Cheng, Yang Zhang, Zhiyu Dai, Genping Wan, Zhonghan Yang, Weibin Cai, Guoquan Gao*, Xia Yang

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Plasminogen Kringle 5(K5) is a proteolytic fragment of plasminogen, which displays potent anti-angiogenic activities. K5 has been shown to induce apoptosis in proliferating endothelial cells; however the exact mechanism has not been well explored. The present study was designed to elucidate the possible molecular mechanism of K5-induced endothelial cell apoptosis. Our results showed that K5 inhibited basic fibroblast growth factors activated in human umbilical vein endothelial cells (HUVECs), indicating proliferation in a dose-dependent manner and induced endothelial cell death via apoptosis. K5 exposure activated caspase 7, 8 and 9. These results suggested that both the intrinsic mitochondrial apoptosis pathway and extrinsic pathway might be involved in K5-induced apoptosis. K5 reduced mitochondrial membrane potential (MMP) of HUVECs, demonstrating mitochondrial depolarization in HUVECs. K5 increased the ratio of Bak to Bcl-xL on mitochondria, decreased the ratio in cytosol, and had no effect on the total amounts of these proteins. K5 also did not effect on Bax/Bcl-2 distribution. K5 increased the ratio of Bak to Bcl-xL on mitochondrial that resulted in mitochondrial depolarization, cytochrome c release and consequently the cleavage of caspase 9. These results suggested that K5 induces endothelial cell apoptosis at least in part via activating mitochondrial apoptosis pathway. The regulation of K5 on Bak and Bcl-xL distribution may play an important role in endothelial cell apoptosis. These results provide further insight into the anti-angiogenesis roles of K5 in angiogenesis-related ocular diseases and solid tumors.

Original languageEnglish (US)
Pages (from-to)846-855
Number of pages10
JournalApoptosis
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2011

Keywords

  • Apoptosis
  • Bak
  • Bcl-2 family
  • Bcl-x
  • Cytochrome c
  • Endothelial cell
  • Kringle 5
  • Mitochondrial membrane potential

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Fingerprint Dive into the research topics of 'Plasminogen K5 activates mitochondrial apoptosis pathway in endothelial cells by regulating Bak and Bcl-x<sub>L</sub> subcellular distribution'. Together they form a unique fingerprint.

  • Cite this

    Gu, X., Yao, Y., Cheng, R., Zhang, Y., Dai, Z., Wan, G., Yang, Z., Cai, W., Gao, G., & Yang, X. (2011). Plasminogen K5 activates mitochondrial apoptosis pathway in endothelial cells by regulating Bak and Bcl-xL subcellular distribution. Apoptosis, 16(8), 846-855. https://doi.org/10.1007/s10495-011-0618-9