EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways.
Homocysteine (Hcy) induced vascular endothelial injury leads to the progression of endothelial dysfunction in atherosclerosis. Epigallocatechin gallate (EGCG), a natural dietary antioxidant, has been applied to protect against atherosclerosis. However, the underlying protective mechanism of EGCG has not been clarified. The present study investigated the mechanism of EGCG protected against Hcy-induced human umbilical vein endothelial cells (HUVECs) apoptosis. Methyl thiazolyl tetrazolium assay (MTT), transmission electron microscope, fluorescent staining, flow cytometry, western blot were used in this study. The study has demonstrated that EGCG suppressed Hcy-induced endothelial cell morphological changes and reactive oxygen species (ROS) generation. Moreover, EGCG dose-dependently prevented Hcy-induced HUVECs cytotoxicity and apoptotic biochemical changes such as reducing mitochondrial membrane potential (MMP), decreasing Bcl-2/Bax protein ratio and activating caspase-9 and 3. In addition, EGCG enhanced the protein ratio of p-Akt/Akt, endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) formation in injured cells. In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy).
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Shumin
S
Liu
Pharmacy Department, Dalian Municipal Central Hospital, Dalian, China.
Zhengwu
Z
Sun
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Peng
P
Chu
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Hailong
H
Li
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Anil
A
Ahsan
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Ziru
Z
Zhou
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Zonghui
Z
Zhang
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Bin
B
Sun
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Jingjun
J
Wu
Pharmacy Department, Dalian Municipal Central Hospital, Dalian, China.
Yalin
Y
Xi
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Guozhu
G
Han
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Yuan
Y
Lin
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China.
Jinyong
J
Peng
Pharmacology Department, Dalian Medical University, west section 9, south road of Lvshun, 116044, Dalian, China. zeyaotang@163.com.
Zeyao
Z
Tang
D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000150:complications / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006710:Homocysteine / Q000633:toxicity; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000178:diet therapy* / Q000235:genetics / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
D000975:Antioxidants; D006710:Homocysteine; D002392:Catechin; C045651:epigallocatechin gallate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
Apoptosis; Epigallocatechin gallate; Homocysteine; Protein kinase B; Reactive oxygen species