Alcohol's Dysregulation of Maternal-Fetal IL-6 and p-STAT3 Is a Function of Maternal Iron Status
Autor: | Kaylee K. Helfrich, Sharon E. Blohowiak, Susan M. Smith, Nipun Saini, George R. Flentke, Pamela J. Kling, Sze Ting Cecilia Kwan, Juna Abazi, Shane M. Huebner |
---|---|
Rok vydání: | 2019 |
Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty animal structures medicine.medical_treatment 030508 substance abuse Medicine (miscellaneous) Stimulation Toxicology Real-Time Polymerase Chain Reaction Article 03 medical and health sciences 0302 clinical medicine Fetus Hepcidin Pregnancy Internal medicine medicine Animals Rats Long-Evans Interleukin 6 STAT3 biology Anemia Iron-Deficiency Ethanol business.industry Interleukin-6 Rats Psychiatry and Mental health Bone morphogenetic protein 6 Disease Models Animal Cytokine Endocrinology Prenatal Exposure Delayed Effects biology.protein Gestation Female 0305 other medical science business 030217 neurology & neurosurgery Iron Dietary Signal Transduction |
Zdroj: | Alcohol Clin Exp Res |
ISSN: | 1530-0277 |
Popis: | BACKGROUND Prenatal alcohol exposure (PAE) causes long-term growth and neurodevelopmental deficits that are worsened by maternal iron deficiency (ID). In our preclinical rat model, PAE causes fetal anemia, brain ID, and elevated hepatic iron via increased maternal and fetal hepcidin synthesis. These changes are normalized by a prenatal iron-fortified (IF) diet. Here, we hypothesize that iron status and PAE dysregulate the major upstream pathways that govern hepcidin production-EPO/BMP6/SMAD and IL-6/JAK2/STAT3. METHODS Pregnant, Long Evans rat dams consumed ID (2 to 6 ppm iron), iron-sufficient (IS, 100 ppm iron), or IF (500 ppm iron) diets and received alcohol (5 g/kg) or isocaloric maltodextrin daily from gestational days (GD) 13.5 to 19.5. Protein and gene expression were quantified in the 6 experimental groups at GD 20.5. RESULTS PAE did not affect Epo or Bmp6 expression, but reduced p-SMAD1/5/8/SMAD1/5/8 protein ratios in both IS and ID maternal and fetal liver (all p's |
Databáze: | OpenAIRE |
Externí odkaz: |