The ABC transporter BCRP/ABCG2 is a placental survival factor, and its expression is reduced in idiopathic human fetal growth restriction

• DOI: 10.1096/fj.07-8688com
• Publication Date: 2007-06-27T00:54:11Z
• Authors: Denis A. Evseenko; Padma Murthi; James W. Paxton; Glen Reid; B. Starling Emerald; K M. Mohankumar; Peter E. Lobie; Shaun P. Brennecke; Bill Kalionis; J. A. Keelan
• Keywords: Abcg2; Trophoblast

The efflux pump ATP binding cassette superfamily member G2 (ABCG2)/breast cancer resistance protein (BCRP) is highly expressed in human placenta. We have investigated the role of BCRP protection placental trophoblasts from apoptosis and its expression idiopathic fetal growth restriction, a condition associated with abnormal apoptosis. Inhibition activity selective inhibitor Ko143 augmented cytokine (tumor necrosis factor-alpha/interferon-gamma)-induced phosphatidylserine externalization primary trophoblast trophoblast-like BeWo cells. Silencing cells significantly increased their sensitivity to apoptotic injury response cytokines exogenous C6 C8 ceramides. silencing also intracellular ceramide levels after exposure but did not affect cellular protoporphyrin IX concentrations or activators intrinsic pathway. placentas pregnancies complicated by restriction was decreased compared controls, suggesting reduced transport substrates conclude that may play hitherto unrecognized survival placenta, protecting against cytokine-induced possibly other extrinsic via modulation signaling. Decreased result viability hence functional deficit, contributing phenotype.