期刊
APOPTOSIS
卷 16, 期 8, 页码 846-855出版社
SPRINGER
DOI: 10.1007/s10495-011-0618-9
关键词
Kringle 5; Apoptosis; Endothelial cell; Bcl-2 family; Mitochondrial membrane potential; Cytochrome c; Bak; Bcl-x(L)
资金
- National Nature Science Foundation of China [30600724, 30700120, 30872980, 30971208, 30973449, 81070746, 81001014]
- National Key Sci-Tech Special Project of China [2008ZX10002-019, 2009ZX09103-642]
- Nature Science Foundation of Guangdong Province, China [10251008901000009]
- Guangdong natural science fund [7002329, 10151008901000007]
- Program for Young Teacher in University [09YKPY73, 10YKPY28]
- Department of health of Guangdong Province [A2008548]
- Health of Guangzhou Municipality [2007-YB-061]
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-x(L) 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-x(L) 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-x(L) 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.
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