kowalski-effectsofearlyonset-2020.pdf (1.5 MB)
The effects of early-onset pre-eclampsia on placental creatine metabolism in the third trimester
journal contribution
posted on 2020-01-01, 00:00 authored by S J Ellery, P Murthi, P A D Gatta, Anthony May, M L Davies-Tuck, Greg KowalskiGreg Kowalski, Damien CallahanDamien Callahan, Clinton BruceClinton Bruce, E M Wallace, D W Walker, H Dickinson, Rod SnowRod SnowCreatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27-40 weeks' gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.
History
Journal
International journal of molecular sciencesVolume
21Issue
3Article number
806Pagination
1 - 14Publisher
MDPILocation
Basel, SwitzerlandPublisher DOI
Link to full text
ISSN
1422-0067eISSN
1422-0067Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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Keywords
Placental bioenergeticsPhosphocreatineMetabolismObstetricsScience & TechnologyLife Sciences & BiomedicinePhysical SciencesBiochemistry & Molecular BiologyChemistry, MultidisciplinaryChemistryplacental bioenergetics 1phosphocreatine 2metabolism 3obstetrics 4GROWTH-HORMONEGLYCINE AMIDINOTRANSFERASEENERGY-METABOLISML-ARGININEEXPRESSIONTRANSPORTPREGNANCIESPLASMAKINASESERUMGenetics
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