Regulation of creatine kinase isoenzymes in human placenta during early, mid-, and late gestation

Thomure, Michael F.; Gast, Michael J.; Srivastava, Neelam; Payne, R. Mark

doi:10.1016/s1071-5576(96)00043-3

Cited by 13 publications

(14 citation statements)

References 26 publications

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“…We confirmed the decrease in creatine phosphate by showing a significant reduction in CK activity in term samples. Our findings complement the data of Thomure et al (1996 ) who found reduced ubiquitous mitochondrial and cytosolic brain CK protein expression in term samples, compared with first and second trimester placentas. We also describe a remarkable increase in the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio towards term.…”

Section: Discussionsupporting

confidence: 90%

Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development

Cindrová‐Davies

Patot

Gardner

et al. 2014

MHR: Basic Science of Reproductive Medicine

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Early human placental and embryonic development occurs in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile in the first, second and third trimesters to determine whether the energy demands are adequately met in the first trimester. We investigated whether hypoxia-inducible factors, HIF-1α and/or HIF-2α, might regulate transcription during the first trimester. First and second trimester tissue was collected using a chorionic villus sampling-like (CVS) technique. Part of each villus sample was frozen immediately and the remainder cultured under 2 or 21% O2 ± 1 mM H2O2, and ±the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1α were assessed by western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT–PCR. Term samples were collected from normal elective Caesarean deliveries. There were no significant differences in concentrations of ADP, NAD+, lactate, and glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1α nor HIF-2α could be detected in time-zero CVS samples. However, culture under any condition (2 or 21% O2 ± 1 mM H2O2) increased HIF-1α and HIF-2α. HIF-1α and HIF-2α were additionally detected in specimens retrieved after curettage. HIF-1α stabilization was accompanied by significant increases in VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by PD169316. In conclusion, our data suggest that first trimester placental tissues are not energetically compromised, and that HIF-1α is unlikely to play an appreciable role in regulating transcriptional activity under steady-state conditions in vivo. However, the pathway may be activated by stress conditions.

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Section: Discussionsupporting

confidence: 90%

Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development

Cindrová‐Davies

Patot

Gardner

et al. 2014

MHR: Basic Science of Reproductive Medicine

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“…Similar to the brain, the amount of TCr measured in the placenta of the spiny mouse increased significantly with advancing pregnancy. Being metabolically very active, it is likely that the placenta itself has a requirement for creatine – creatine kinase expression, which is tightly coupled with cellular energy requirements, peaks in term human placenta [ 39 ]. However, as for the human placenta [ 4 ], it appears that this organ itself does not synthesize creatine, as we were unable to detect either AGAT or GAMT mRNA or protein in the placenta of the spiny mouse from mid-gestation to term.…”

Section: Discussionmentioning

confidence: 99%

Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse

et al. 2009

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Background: Creatine synthesis takes place predominately in the kidney and liver via a two-step process involving AGAT (L-arginine:glycine amidinotransferase) and GAMT (guanidinoacetate methyltransferase). Creatine is taken into cells via the creatine transporter (CrT), where it plays an essential role in energy homeostasis, particularly for tissues with high and fluctuating energy demands. Very little is known of the fetal requirement for creatine and how this may change with advancing pregnancy and into the early neonatal period. Using the spiny mouse as a model of human perinatal development, the purpose of the present study was to comprehensively examine the development of the creatine synthesis and transport systems.

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“…Cr is thought to be actively transported across the placenta from maternal circulation during pregnancy, with placental Cr transporter expression evident as early as 13 weeks of gestation [ 62 ]. Expression of mitochondrial and cytosolic CK enzymes in the placenta is highly coordinated and markedly increased in the third trimester, concomitant with increased metabolic activity of the placenta in late pregnancy [ 63 ]. It remains unclear when the human fetal reno-hepatic axis for endogenous Cr synthesis is established, although studies in the precocial spiny mouse indicate that this axis develops late in gestation [ 64 ].…”

Section: Creatine and Perinatal Hypoxic Ischemic Injurymentioning

confidence: 99%

Creatine kinase in ischemic and inflammatory disorders

Kitzenberg

Colgan

Glover

2016

Clinical & Translational Med

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The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress. In these settings, creatine and phosphocreatine prevent depletion of intracellular ATP and internal acidification, enhance post-ischemic recovery of protein synthesis and promote free radical scavenging and stabilization of cellular membranes. The creatine kinase energy system is itself further regulated by hypoxic signaling, highlighting the existence of endogenous mechanisms in mammals that can enhance creatine metabolism during oxygen deprivation to promote tissue resolution and homeostasis. Here, we review recent insights into the creatine kinase pathway, and provide rationale for dietary creatine supplementation in human ischemic and inflammatory pathologies.

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Regulation of creatine kinase isoenzymes in human placenta during early, mid-, and late gestation

Cited by 13 publications

References 26 publications

Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development

Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development

Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse

Creatine kinase in ischemic and inflammatory disorders

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