title: Analysis of endoplasmic reticulum stress in placentas of HIV-infected women treated with protease inhibitors.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany. Electronic address: ansgar.bruening@med.uni-muenchen.de.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Brüning
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kimmich
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: German J
authors.initials: GJ
authors.lastname: Brem
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Marie L
authors.initials: ML
authors.lastname: Buchholtz
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Mylonas
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kost
authors.affiliation: Department of Obstetrics and Gynecology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Weizsäcker
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gingelmaier
mesh_terms: D000328:Adult; D001343:Autophagy; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D017320:HIV Protease Inhibitors; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human
keywords: Adverse effect; Endoplasmic reticulum stress; Mother-to-child transmission; Placenta; Protease inhibitor; XBP1