The role of non-synonymous NPY gene polymorphism in the nitric oxide production in HUVECs.
A Leu7Pro change in the signal peptide of preproNPY is a functional substitution, which changes the processing of NPY in cells and associates with several cardiovascular and metabolic conditions in humans. The current study investigates the effect of the P7 allele in endothelial cells, where decreased nitric oxide (NO) production is a promoting factor to endothelial dysfunction. The function of NO system was assessed in the human umbilical vein endothelial cells (HUVECs) with [p.L7]+[p.L7] or [p.L7]+[p.P7] genotype. NPY seems to have a significant influence on NO system in HUVECs, and the responses are time and genotype dependent. HUVECs with [p.L7]+[p.P7] genotype seem to have higher basal production of NO, but after a long term treatment with NPY these cells express less eNOS mRNA and overall eNOS protein levels are lower. These significant differences in the NO bioavailability may explain the association of the L7P polymorphism with several cardiovascular complications.
Kaipio
Katja
K
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Finland.
Vahlberg
Tero
T
Suominen
Marianne
M
Pesonen
Ullamari
U
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D014471:Umbilical Veins / Q000378:metabolism
D009478:Neuropeptide Y; D012333:RNA, Messenger; D009569:Nitric Oxide; D011392:Proline; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D007930:Leucine