Antenatal betamethasone (BM) therapy for women in jeopardy of premature delivery accelerates the lung development in preterm infants and reduces infant mortality rates, but may induce early programming events with chronic cardiovascular consequences. In a sheep model of fetal programming, in utero BM-exposed (BMX) offspring as adults exhibit elevated mean arterial pressure (MAP), decreased baroreflex sensitivity (BRS) for the control of heart rate and insulin resistance accompanied by dysregulation of the brain renin–angiotensin (Ang) system (RAS). However, the status of signaling mechanisms in the brain dorsomedial medulla (DMM) of the BMX sheep that comprise both the mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) cellular pathways is unknown. Given the importance of these signaling pathways in the actions of Ang peptides as well as baroreflex function and autonomic integration, we applied both a kinase signaling array and associated individual immunoblots of the dorsomedial brain medulla from adult female and male sheep with antenatal BMX. MAPK and PI3K pathways were altered significantly in the BMX sheep in a sex-dependent manner. A protein array for kinases (PathScan® Intracellular Signaling Array Kit, Cell Signaling) and subsequent verification by immunoblot revealed that within the DMM, female BMX sheep exhibit lower expression of proteins in the PI3K pathway, while male BMX sheep show greater expression of p-MAPK pathway proteins extracellular signal regulated kinase (ERK) 1/2. We conclude that maladaptive changes in these two kinase pathways in the DMM may contribute to the chronic dysregulation of blood pressure in this model of fetal programming.
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A scanning electron micrograph (digitally altered and colourized, 4000× magnification) depicting a mesenchymal stem cell (orange) encapsulated in a self-assembling peptide hydrogel. In volume 132, issue 17 of Clinical Science, McFetridge et al. discuss the use of hydrogel materials to unlock the potential of stem cell therapy to treat chronic kidney disease. This image was provided by the authors and produced in collaboration with Dr Simon Crawford at the Ramaciotti Centre for Cryo-Electron Microscopy, and the Monash Teaching Resource Support Unit.
Research Article|
September 14 2018
Sex-dependent expression of brain medullary MAP and PI3 kinases in adult sheep with antenatal betamethasone exposure
Alexa S. Hendricks;
Alexa S. Hendricks
1Department of Surgery, Hypertension and Vascular Research, Cardiovascular Sciences Center, Wake Forest University School of Medicine, Winston-Salem, NC, U.S.A.
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Hossam A. Shaltout;
Hossam A. Shaltout
1Department of Surgery, Hypertension and Vascular Research, Cardiovascular Sciences Center, Wake Forest University School of Medicine, Winston-Salem, NC, U.S.A.
2Department of Obstetrics and Gynecology, Wake Forest School of Medicine, Winston Salem, NC, U.S.A.
3Department of Pharmacology and Toxicology, School of Pharmacy, Alexandria University, Alexandria, Egypt
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Brain M. Westwood;
Brain M. Westwood
1Department of Surgery, Hypertension and Vascular Research, Cardiovascular Sciences Center, Wake Forest University School of Medicine, Winston-Salem, NC, U.S.A.
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Mark C. Chappell;
Mark C. Chappell
1Department of Surgery, Hypertension and Vascular Research, Cardiovascular Sciences Center, Wake Forest University School of Medicine, Winston-Salem, NC, U.S.A.
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Debra I. Diz
1Department of Surgery, Hypertension and Vascular Research, Cardiovascular Sciences Center, Wake Forest University School of Medicine, Winston-Salem, NC, U.S.A.
Correspondence: Debra I. Diz ([email protected])
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Publisher: Portland Press Ltd
Received:
May 18 2018
Revision Received:
July 04 2018
Accepted:
July 19 2018
Accepted Manuscript online:
July 19 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (17): 1953–1962.
Article history
Received:
May 18 2018
Revision Received:
July 04 2018
Accepted:
July 19 2018
Accepted Manuscript online:
July 19 2018
Citation
Alexa S. Hendricks, Hossam A. Shaltout, Brain M. Westwood, Mark C. Chappell, Debra I. Diz; Sex-dependent expression of brain medullary MAP and PI3 kinases in adult sheep with antenatal betamethasone exposure. Clin Sci (Lond) 14 September 2018; 132 (17): 1953–1962. doi: https://doi.org/10.1042/CS20180417
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