Cadmium reduces nitric oxide production by impairing phosphorylation of endothelial nitric oxide synthase.
Cadmium (Cd) perturbs vascular health and interferes with endothelial function. However, the effects of exposing endothelial cells to low doses of Cd on the production of nitric oxide (NO) are largely unknown. The objective of the present study was to evaluate these effects by using low levels of CdCl2 concentrations, ranging from 10 to 1000 nmol/L. Cd perturbations in endothelial function were studied by employing wound-healing and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. The results suggest that a CdCl2 concentration of 100 nmol/L maximally attenuated NO production, cellular migration, and energy metabolism in endothelial cells. An egg yolk angiogenesis model was employed to study the effect of Cd exposure on angiogenesis. The results demonstrate that NO supplementation restored Cd-attenuated angiogenesis. Immunofluorescence, Western blot, and immuno-detection studies showed that low levels of Cd inhibit NO production in endothelial cells by blocking eNOS phosphorylation, which is possibly linked to processes involving endothelial function and dysfunction, including angiogenesis.
Majumder
Syamantak
S
Vascular Biology Lab, Life Sciences, AU-KBC Research Centre, MIT Campus, Anna University, Chennai, Tamil Nadu, India.
Muley
Ajit
A
Kolluru
Gopi Krishna
GK
Saurabh
Samir
S
Tamilarasan
K P
KP
Chandrasekhar
Sidhharth
S
Reddy
Hima Bindu
HB
Purohit
Sharad
S
Chatterjee
Suvro
S
D000818:Animals; D019256:Cadmium Chloride / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004530:Egg Yolk / Q000166:cytology / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013385:Succinate Dehydrogenase; D019256:Cadmium Chloride; D002118:Calcium