Analysis of endoplasmic reticulum stress in placentas of HIV-infected women treated with protease inhibitors

作者：Bruening Ansgar; Kimmich Tanja; Brem German J; Buchholtz Marie L; Mylonas Ioannis; Kost Bernd; Weizsaecker Katharina; Gingelmaier Andrea

来源：Reproductive Toxicology, 2014, 50: 122-128.

DOI：10.1016/j.reprotox.2014.10.012

• Protease inhibitor
• Placenta
• XBP1
• Endoplasmic reticulum stress
• Adverse effect
• Mother-to-child transmission

Combined antiretroviral therapy has proven efficacy in decreasing vertical HIV transmission. However, endoplasmic reticulum stress is a known side effect of HIV protease inhibitors. We investigated endoplasmic reticulum stress in placentas of HIV-infected and uninfected mothers by PCR-based splicing analysis of the specific endoplasmic reticulum stress marker XBP1 in post-delivery placental samples of uninfected mothers and in HIV-infected mothers taking antiretroviral therapy. No elevated XBP1 splicing could be detected in placentas of uninfected mothers and most of the mothers receiving combined anti-retroviral therapy. However, markedly elevated XBP1 splicing was found in the placentas of three individuals on combined antiviral therapy, all receiving lopinavir or atazanavir. In vitro experiments confirmed induction of endoplasmic reticulum stress by lopinavir and atazanavir in trophoblast-derived cell lines. Since endoplasmic reticulum stress occurred in selective patients only, individual differences in susceptibility of HIV-infected mothers to protease inhibitor induced endoplasmic reticulum stress can be postulated.

• 出版日期2014-12