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Vascular Signaling Pathways for Bisphenol A
Author(s) -
Omorebokhae Joanne Izevbua,
Munyu Sarah,
Oyekan Adebayo O,
Yakubu Momoh A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1050.16
Subject(s) - endocrinology , medicine , chemistry , enos , apocynin , signal transduction , biology , biochemistry , nitric oxide , oxidative stress , nadph oxidase , nitric oxide synthase
Bisphenol A (BPA has been implicated in varied toxic effects but with limited understanding of the mode of actions leading to cellular and vascular dysfunction. Using the whole rat and cerebral micovascular endothelial cells (EC), we investigated the possible signaling pathways for BPA. The effects of BPA (160 mg/kg in feed8 weeks) were determined on blood glucose, tissue perfusion, plasma, and urine NO and bilirubin. Signaling pathways for BPA was determined in EC derived from piglet's brain. Confluent cells received BPA (10 −8 − 10 −4 M) in the presence or absence of calphostin C (10 −5 M), tyrphostin (10 −5 M), Apocynin (10 −4 M); NO and ET‐1 levels were determined in the media and cells analyzed for protein expression. In the animal studies, BPA elevated blood glucose from 81 ± 6 to 92 ± 4 mg/dL, urinary bilirubin from 599±30 to 1047±154 μM/mL as well as urinary excretion of NO. Tissue eNOS, p phox22 and NF‐kB protein expression were elevated in BPA‐treated rats. In EC, BPA increased NO levels none dose‐dependently which was enhanced by pretreatment with tyrphostin but not with apocynin at 12 hrs but longer BPA (24 hrs) in the presence of apocyinin increased NO level. BPA increased ET‐1 production as well as eNOS protein expression. These results inconclusively indicate that BPA could adversely affect diverse vascular signaling pathways possibly involving eNOS, ROS, protein tyrosine kinase and NF‐kB in EC. The effects of these changes on adverse vascular functions are yet to be fully linked and would require a longer treatment time.