Proceedings of The Physiological Society
AstraZeneca (2010) Proc Physiol Soc 18, PC24
Does ethanol promote endoplasmic reticulum stress-induced cell death during pregnancy: a study on involvement of oxidative stress?
S. Kesireddy1,2, G. Burton2
1. Zoology, sri Venkateswara University, Tirupati, andhra Pradesh, India. 2. Department of Physiology,Development and Neuroscience, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
When pregnant woman drink, alcohol reaches the baby through the placenta. However, the baby cannot process it as fast as the mother can, so it is exposed to greater amounts of alcohol for longer than the mother, which can seriously affect the baby's development and it may also lead to miscarriage (1,2). Oxidative stress is central to alcohol-induced cell death during pregnancy (3,4). The underlying cellular/molecular mechanisms remain unclear. The role of the endoplasmic reticulum (ER) in this process is uncertain. In ER signalling, PERK-Nrf2 and Ire-CHOP are two pathways that determine cell fate under stress (5). Using human choriocarcinoma JEG-3 cells, we explored ER stress response induced experimentally by treatment with different doses of ethanol (100 mg to 800 mg/ml) and tunicamycin (0.125 to 1 μg/ml). We demonstrated that exposure to ethanol alone had little effect on the expression of markers for ER stress; however, ethanol drastically enhanced the expression of GRP78, CHOP, ATF4, ATF6 and phosphorylated PERK and elF2-alpha when induced by tunicamycin. We speculate that sustained ER stress may contribute to the placental dysfunction seen in human pregnancy complications. However, further studies are required to elucidate whether ethanol promotes ER stress-induced cell death in the placenta during pregnancy.
Where applicable, experiments conform with Society ethical requirements