Role of estrogenic compounds (diethylstibestrol, 17β‐estradiol, and bisphenol A) in the phosphorylation of substrate by protein kinase Cα

Abstract

Estrogenic compounds can activate protein kinase C (PKC), which is a calcium and phospholipid-dependent serine/threonine kinase. In the present study, we investigated the role of 17beta-estradiol (E2), diethylstibestrol (DES), and bisphenol A (BPA) in the phosphorylation of substrate by PKCalpha using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The level of phosphorylated peptide was low in the absence of phosphatidylserine (PS). Moreover, reduction of phosphorylation ratios was identified in the presence of diacylglycerol (DAG) and Ca(2+) or PS and Ca(2+) after adding E2, DES, and BPA. However, no change in phosphorylation ratios was found in the presence of DAG and PS. Addition of E2, DES, and BPA also had no influence on the phosphorylation reaction of substrate by cell or tissue lysate samples. Our study suggests that E2, DES, and BPA can bind to the C2 domain of PKCalpha but have no effects on the phosphorylation reaction of substrates in the presence of DAG and PS.

Vascular Effects of Phytoestrogens and Alternative Menopausal Hormone Therapy in Cardiovascular Disease

“…During cell activation, PKC translocation to the cell surface may trigger a cascade of protein kinases that ultimately interact with the contractile myofilaments and cause VSM contraction [141]. E2 inhibits PKC [142] and decreases the myofilament sensitivity to [Ca 2+ ] i [143]. PKC activity may also be modulated by phytoestrogens [144], and the effects of phytoestrogens on PKC-dependent pathways need to be further investigated.…”