Estradiol pretreatment attenuated nicotine-induced endothelial cell apoptosis via estradiol functional membrane receptor.
Cigarette smoking is highly associated with increased cardiovascular disease complications. The female population, however, manifests reduced cardiovascular morbidity. We define nicotine's effect upon human umbilical vein endothelial cells (HUVECs), determine whether estradiol might ameliorate endothelial dysfunction via its membrane estrogen receptor (mER), and attempt to elucidate the underlying mechanisms. Endothelial cells were pretreated with estradiol-BSA and measured resultant ion flux across the cells via the patch clamp technique to assess mER is functionality. Estradiol-BSA administration was associated with 30% decreased nicotine-induced apoptosis and also attenuated nicotine-activated phosphorylation of p38 and ERK. Pretreatment of estradiol-BSA triggered a low calcium influx, suggesting ahead low influx calcium played a critical role in the underlying protective mechanisms of estradiol. Furthermore, this estradiol-BSA protection against apoptosis remained effective in the presence of tamoxifen, an intracellular estrogen receptor (iER) inhibitor. Additionally, tamoxifen did not abolish estradiol-BSA's inhibitory effect upon p38 and ERK's activation, giving evidence to the obligatory role of p38 and ERK signaling in the estradiol-BSA's anti-apoptotic action via mER. Our study provides evidence that nicotine enhances endothelial cell apoptosis, but estrogen exerts anti-apoptotic effect through its functional membrane estrogen receptor. Clinically, the nicotine in cigarettes might contribute to endothelial dysfunction, whereas ambient estradiol may provide cellular protection against nicotine-induced injury through its functional membrane receptor via MAPK pathway downregulation.
Department of Anesthesiology, Shanxi Medical University, 56 South Xinjian Road, Taiyuan, Shanxi, China.
Li-li
LL
Wang
Jian-li
JL
Zhao
Wayne-Bond
WB
Lau
Yan-qing
YQ
Zhang
Zhong-dong
ZD
Qiao
Ya-jing
YJ
Wang
D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009538:Nicotine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D011959:Receptors, Estradiol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012306:Risk; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013629:Tamoxifen / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D011959:Receptors, Estradiol; D013629:Tamoxifen; D004958:Estradiol; D009538:Nicotine; D048051:p38 Mitogen-Activated Protein Kinases