Ginkgo biloba extract reduces endothelial progenitor-cell senescence through augmentation of telomerase activity.
Our previous studies have shown that Ginkgo biloba extract increased endothelial progenitor-cell (EPC) numbers and functional activity. However, the mechanisms remain to be determined. Recent studies have demonstrated that increased EPC numbers and activity were associated with the inhibition of EPC senescence, which involved activation of telomerase. Therefore, we investigated whether Ginkgo biloba extract inhibited the onset of EPC senescence through telomerase activation, leading to potentiation of cellular activity. After ex vivo cultivation, EPCs became senescent as determined by acidic ss-galactosidase staining. Ginkgo biloba extract dose-dependently prevented the onset of EPC senescence in culture. Moreover, Ginkgo biloba extract increased proliferation of EPCs as assessed by MTT assay and colony-forming capacity. To get further insights into the underlying mechanisms of these effects, we measured telomerase activity and determined the phosphorylation of Akt by Western blotting. Ginkgo biloba extract significantly increased telomerase activity and phosphorylation of the serine/threonine protein kinase Akt, a downstream effector of phosphoinositide 3-kinase (PI3K). Moreover, pretreatment with PI3K inhibitor, LY294002, significantly attenuated the Ginkgo biloba extract-induced telomerase activity. Taken together, the results indicated that Ginkgo biloba extract delayed the onset of EPC senescence, which may be related to activation of telomerase through the PI3k/Akt signaling pathway. The inhibition of EPC senescence by Ginkgo biloba extract in vitro may improve the functional activity of EPCs in a way that is important for potential cell therapy.
Dong
Xie Xu
XX
Department of Cardiology, the First Affiliated Hospital, Medical School of Zhejiang University, Hangzhou, China.
Hui
Zhu Jun
ZJ
Xiang
Wang Xing
WX
Rong
Zhang Fu
ZF
Jian
Sun
S
Zhu
Chen Jun
CJ
D015153:Blotting, Western; D016922:Cellular Senescence / Q000187:drug effects*; D002999:Clone Cells / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D020441:Ginkgo biloba / Q000737:chemistry*; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000201:enzymology*; D019098:Telomerase / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D001616:beta-Galactosidase / Q000378:metabolism
D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D019098:Telomerase; D001616:beta-Galactosidase; C022616:thiazolyl blue