Maternal nicotine exposure leads to impaired disulfide bond formation and augmented endoplasmic reticulum stress in the rat placenta
| Autor: | Catherine J. Nicholson, Alison C. Holloway, Michael K. Wong, Daniel B. Hardy |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Nicotine Science Placenta RNA Splicing Medical Physiology Protein Disulfide-Isomerases Apoptosis Regulatory Factor X Transcription Factors Placental insufficiency Biology fetal outcomes Pregnancy Internal medicine medicine Animals Amino Acids Protein disulfide-isomerase Hypoxia Fetus Multidisciplinary Endoplasmic reticulum Pharmacy and Pharmaceutical Sciences medicine.disease Endoplasmic Reticulum Stress Rats rats DNA-Binding Proteins Endocrinology medicine.anatomical_structure Gene Expression Regulation Maternal Exposure Unfolded protein response Unfolded Protein Response Medicine Female Signal transduction Oxidoreductases Biomarkers Transcription Factor CHOP nicotine medicine.drug Signal Transduction Transcription Factors Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 3, p e0122295 (2015) Physiology and Pharmacology Publications |
| ISSN: | 1932-6203 |
| Popis: | Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation--a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar rats received daily subcutaneous injections of either saline (vehicle) or nicotine bitartrate (1 mg/kg) for 14 days prior to mating and during pregnancy. Placentas were harvested on embryonic day 15 for analysis. Protein and mRNA expression of markers involved in ER stress (e.g., phosphorylated eIF2α, Grp78, Atf4, and CHOP), disulfide bond formation (e.g., PDI, QSOX1, VKORC1), hypoxia (Hif1α), and amino acid deprivation (GCN2) were quantified via Western blot and/or Real-time PCR. Maternal nicotine exposure led to increased expression of Grp78, phosphorylated eIF2α, Atf4, and CHOP (p |
| Databáze: | OpenAIRE |
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