Ginkgo biloba extract EGB761 protects against aging-associated diastolic dysfunction in cardiomyocytes of D-galactose-induced aging rat.
The aim of the present study was to make use of the artificially induced aging model cardiomyocytes to further investigate potential anti-aging-associated cellular diastolic dysfunction effects of EGB761 and explore underlying molecular mechanisms. Cultured rat primary cardiomyocytes were treated with either D-galactose or D-galactose combined with EGB761 for 48 h. After treatment, the percentage of cells positive for SA-β-gal, AGEs production, cardiac sarcoplasmic reticulum calcium pump (SERCA) activity, the myocardial sarcoplasmic reticulum calcium uptake, and relative protein levels were measured. Our results demonstrated that in vitro stimulation with D-galactose induced AGEs production. The addition of EGB761 significantly decreased the number of cells positive for SA-β-gal. Furthermore, decreased diastolic [Ca(2+)](i), curtailment of the time from the maximum concentration of Ca(2+) to the baseline level and increased reuptake of Ca(2+) stores in the SR were also observed. In addition, the level of p-Ser16-PLN protein as well as SERCA was markedly increased. The study indicated that EGb761 alleviates formation of AGEs products on SERCA2a in order to mitigate myocardial stiffness on one hand; on other hand, improve SERCA2a function through increase the amount of Ser16 sites PLN phosphorylation, which two hands finally led to ameliorate diastolic dysfunction of aging cardiomyocytes.
Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Jing
J
Liu
Junhong
J
Wang
Xiangjian
X
Chen
Changqing
C
Guo
Yan
Y
Guo
Hui
H
Wang
D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005690:Galactose / Q000633:toxicity; D020441:Ginkgo biloba / Q000737:chemistry*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D000099211:Phospholamban; D000096983:Ginkgo Extract
D002118:Calcium; D002135:Calcium-Binding Proteins; D005690:Galactose; D017127:Glycation End Products, Advanced; D010936:Plant Extracts; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract