Tongxinluo improves anti-hypoxia ability of vascular endothelial cells via PI-3K/Akt/HIF pathway |
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Authors: | LIANG Jun-qing XU Hai-bo CHEN Xiao-juan XING Zhi-jun YIN Bei-pei WU Kun ZHANG Zi-qian ZHOU Li-tao WU Yi-ling |
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Institution: | 1. Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang 050035, China;2. Affiliated Hospital of Chengde Medical College, Chengde 067000, China;3. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai 200438, China;4. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China |
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Abstract: | AIM: To investigate the effects of PI-3K/Akt/HIF pathway on anti-hypoxia ability of vascular endothelial cells influenced by Tongxinluo under hypoxic condition. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into the following groups: control group, Tongxinluo (100 mg/L) group, hypoxia group and hypoxia+Tongxinluo (100 mg/L) group. The CCK-8 assay were used to detect the viability and proliferation rate of the cells in each group. The protein levels of HIF-1α, Bcl-2, Mcl-1, Bax and phosphorylated Akt were studied by immunoblotting analysis. The HUVECs were transiently transfected with the dominant negative mutant of HIF-1α (DN-HIF). The apoptotic rates were analyzed by flow cytometry (FCM). The HUVECs were transiently transfected with the dominant negative mutant of PI-3K (Δp85) or Akt (DN-Akt) to investigate the role of PI-3K/Akt signal pathway in the anti-hypoxia ability of Tongxinluo on endothelial cells. RESULTS: Under hypoxic condition, although the proliferation rate increased significantly in Tongxinluo group compared with hypoxia group, the degree was notably weak compared with control group. The protein levels of HIF-1α, Bcl-2, Mcl-1 and phosphorylated Akt were up-regulated by Tongxinluo. Meanwhile, the expression of Bax was down-regulated. Inhibition of HIF-1α activation by DN-HIF and inhibition of the PI-3K/Akt pathway by Δp85 or DN-Akt attenuated the increase in HIF-1α expression and HUVEC viability induced by Tongxinluo. The percentage of apoptotic HUVECs was down-regulated to a certain extent by Tongxinluo. CONCLUSION: Tongxinluo improves the anti-hypoxia ability of vascular endothelial cells by up-regulating the protein level of HIF-1α, promoting the expression of anti-apoptotic factors, improving the cell viability and eventually reducing the apoptotic rate.These effects of Tongxinluo depend on PI-3K/Akt signal pathway. |
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Keywords: | Tongxinluo Hypoxia-inducible factor Vascular endothelial cells Signal transduction Hypoxic injury |
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