scholarly journals The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

2020 ◽  
Vol 21 (3) ◽  
pp. 806 ◽  
Author(s):  
Stacey J. Ellery ◽  
Padma Murthi ◽  
Paul A. Della Gatta ◽  
Anthony K. May ◽  
Miranda L. Davies-Tuck ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Early Onset ◽  
Energy Homeostasis ◽  
Metabolic Dysfunction ◽  
Third Trimester ◽  
Creatine Transporter ◽  
Protein Levels ◽  
Total Creatine ◽  
Spatio Temporal ◽  
Creatine Metabolism

Creatine 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.

Placental creatine metabolism in cases of placental insufficiency and reduced fetal growth

2019 ◽  
Vol 25 (8) ◽  
pp. 495-505 ◽  
Author(s):  
Stacey J Ellery ◽  
Padma Murthi ◽  
Miranda L Davies-Tuck ◽  
Paul A Della Gatta ◽  
Anthony K May ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Fetal Growth ◽  
Low Birthweight ◽  
Chorionic Villus ◽  
First Trimester ◽  
Late Gestation ◽  
Amino Acid Transporters ◽  
Third Trimester ◽  
The Third ◽  
Creatine Metabolism

Abstract Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate—GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

scholarly journals Birdsong Decreases Protein Levels of FoxP2, a Molecule Required for Human Speech

2008 ◽  
Vol 100 (4) ◽  
pp. 2015-2025 ◽  
Author(s):  
Julie E. Miller ◽  
Elizabeth Spiteri ◽  
Michael C. Condro ◽  
Ryan T. Dosumu-Johnson ◽  
Daniel H. Geschwind ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Vocal Learning ◽  
Brain Regions ◽  
Motor Deficits ◽  
Mrna Levels ◽  
Adult Males ◽  
Protein Levels ◽  
Area X

Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

scholarly journals Galanin inhibits leptin expression and secretion in rat adipose tissue and 3T3-L1 adipocytes

2004 ◽  
Vol 33 (1) ◽  
pp. 11-19 ◽  
Author(s):  
RY Li ◽  
HD Song ◽  
WJ Shi ◽  
SM Hu ◽  
YS Yang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Vital Role ◽  
Dependent Manner ◽  
Protein Levels ◽  
Orexigenic Peptide ◽  
Fat Depot ◽  
Rat Adipose Tissue ◽  
Leptin Expression

In addition to serving as a fat depot, adipose tissue is also considered as an important endocrine organ that synthesizes and secretes a number of factors. Leptin is an adipocyte-derived hormone that plays a vital role in energy balance. Expression of leptin is regulated by dietary status and hormones. In the present study, we report that galanin, an orexigenic peptide, inhibits leptin expression and secretion in rat adipose tissue and in 3T3-L1 adipocytes. Treatment with galanin (25 micro g/animal) induced approximately 46% down-regulation of leptin secretion at 15 min, followed by 40, 37 and 47% decreases in leptin secretion at 1, 2 and 4 h respectively. Although Northern blot analysis of adipose tissue from the same animals showed that leptin mRNA expression in adipose tissue was unaffected by galanin treatment for 2 h, galanin treatment for 4 h led to decline of leptin mRNA expression in a dose-dependent manner. Meanwhile, treating the rats with galanin had no effect on leptin mRNA expression in the hypothalamus. The inhibitory action of the galanin on leptin mRNA and protein levels was also observed in vitro. When incubated with 10 nM galanin for 48 h, leptin mRNA expression and protein secretion also decreased in 3T3-L1 adipocytes. On the other hand, galanin was found not only to express in rat adipose tissue, but also to increase about 8-fold after fasting. Based on these data, we speculate that increased galanin expression in rat adipose tissue after fasting may be involved in reducing leptin expression and secretion in fasting rats.

The effect of maternal vitamin D supplementation in the third trimester on the incidence of early-onset sepsis in their newborns

2020 ◽  
Vol 9 (2) ◽  
pp. 74
Author(s):  
Prathapa Shetty ◽  
Manasee Deka ◽  
ManojKumar Yadav ◽  
Geeta Gathwala ◽  
Sunny Lohia ◽  
...  
Keyword(s):  
Vitamin D ◽  
Early Onset ◽  
Vitamin D Supplementation ◽  
Third Trimester ◽  
Maternal Vitamin ◽  
The Third ◽  
Early Onset Sepsis

Unilateral labyrinthectomy induced changes on GDNF receptor complex proteins in the rat medial vestibular nuclei

2007 ◽  
Vol 16 (4-5) ◽  
pp. 171-177
Author(s):  
Adrian Lozada ◽  
Kaj Karlstedt ◽  
Pertti Panula ◽  
Antti A. Aarnisalo
Keyword(s):  
Mrna Expression ◽  
Vestibular Nucleus ◽  
Medial Vestibular Nucleus ◽  
Receptor Complex ◽  
Trophic Effect ◽  
Expression Levels ◽  
Protein Levels ◽  
Unilateral Labyrinthectomy ◽  
Ganglion Neurons ◽  
Mrna Expression Levels

In the auditory periphery, GDNF has been shown to have a trophic effect to spiral ganglion neurons, both during development and in adult animals. We have studied the effect of unilateral labyrinthectomy (UL) on protein levels and expression of GDNF multicomponent receptor complex: the ret tyrosine kinase and coreceptor GFRα-1 in the medial vestibular nucleus of the adult rat. GFRα-1 protein levels display an increasing trend in ipsilateral medial vestibular nucleus culminating at 48 h post UL. On the other hand, GFRα-1 mRNA expression levels in ipsi- and contralateral medial vestibular nucleus show a steadily decreasing trend that is significant at 1 week post-lesion. Protein levels for c-Ret isoforms also show an initial bilateral decreasing trend that ceases at 48 h in ipsilateral medial vestibular nucleus but persists on the contralateral side. c-Ret mRNA expression levels show a significant decrease at 4 h post UL followed by another significant decrease 1 week post UL. Our data would suggest that neurotrophins belonging to the GDNF family are involved in this model of post-lesional CNS plasticity.

scholarly journals Adenosine upregulates VEGF expression in cultured myocardial vascular smooth muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. H595-H602 ◽  
Author(s):  
Jian-Wei Gu ◽  
Ann L. Brady ◽  
Vivek Anand ◽  
Michael C. Moore ◽  
Whitney C. Kelly ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Vascular Smooth Muscle Cells ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Vegf Mrna Expression ◽  
Vegf Protein

We tested whether adenosine has differential effects on vascular endothelial growth factor (VEGF) expression under normoxic and hypoxic conditions, and whether A1 or A2 receptors (A1R; A2R) mediate these effects. Myocardial vascular smooth muscle cells (MVSMCs) from dog coronary artery were exposed to hypoxia (1% O2) or normoxia (20% O2) in the absence and presence of adenosine agonists or antagonists for 18 h. VEGF protein levels were measured in media with ELISA. VEGF mRNA expression was determined with Northern blot analysis. Under normoxic conditions, the adenosine A1R agonists, N 6-cyclopentyladenosine and R(-)- N 6-(2-phenylisopropyl)adenosine did not increase VEGF protein levels at A1R stimulatory concentrations. However, adenosine (5 μM) and the adenosine A2R agonist N 6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]ethyl adenosine (DPMA; 100 nM) increased VEGF protein levels by 51 and 132% and increased VEGF mRNA expression by 44 and 90%, respectively, in cultured MVSMCs under normoxic conditions. Hypoxia caused an approximately fourfold increase in VEGF protein and mRNA expression, which could not be augmented with exogenous adenosine, A2R agonist (DPMA), or A1R agonist [1,3-diethyl-8-phenylxanthine (DPX)]. The A2R antagonist 8-(3-chlorostyryl)-caffeine completely blocked adenosine-induced VEGF protein and mRNA expression and decreased baseline VEGF protein levels by up to ∼60% under normoxic conditions but only by ∼25% under hypoxic conditions. The A1R antagonist DPX had no effect. These results are consistent with the hypothesis that 1) adenosine increases VEGF protein and mRNA expression by way of A2R. 2) Adenosine plays a major role as an autocrine factor regulating VEGF expression during normoxic conditions but has a relatively minor role during hypoxic conditions. 3) Endogenous adenosine can account for the majority of basal VEGF secretion by MVSMCs under normoxic conditions and could therefore be a maintenance factor for the vasculature.

Lower antioxidant capacity in the prefrontal cortex of individuals with schizophrenia

2017 ◽  
Vol 52 (7) ◽  
pp. 690-698 ◽  
Author(s):  
Yiru Zhang ◽  
Vibeke Sørensen Catts ◽  
Cynthia Shannon Weickert
Keyword(s):  
Prefrontal Cortex ◽  
Antioxidant Capacity ◽  
Mrna Expression ◽  
Antioxidant System ◽  
Messenger Rna ◽  
Total Glutathione ◽  
Protein Levels ◽  
Significant Difference ◽  
Dorsolateral Prefrontal ◽  
And Control

Objective: The glutathione (GSH) pathway is the main antioxidant system to protect against oxidative stress in the human brain. In this study, we tested whether molecular components of the GSH antioxidant system are changed in dorsolateral prefrontal cortex tissue from people with schizophrenia compared to controls. Method: The levels of total glutathione and reduced GSH were determined by fluorometric assay via quantifying thiols in extracts from frontal cortex of 68 people. Immunoblotting was used to measure levels of enzymes responsible for maintaining GSH, the glutamyl-cysteine ligase (GCL) catalytic subunit (GCLC) and the GSH peroxidase (GPx)-like protein ( n = 74). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure GCLC messenger RNA (mRNA) expression. Results: Both total glutathione ( t(66) = 2.467, p = 0.016) and reduced GSH ( t(66) = 3.001, p = 0.004) levels were significantly less in people with schizophrenia than in controls. However, there were no significant differences in either GCLC-like protein ( t(72) = −1.077, p = 0.285) or GCLC mRNA expression ( t(71) = −0.376, p = 0.708) between people with schizophrenia and control subjects. There was also no significant difference of GPx-like protein levels between schizophrenia and controls ( t(72) = −0.060, p = 0.952). Moreover, no significant correlations of putative confounding factors with GSH changes were detected. Discussion: These results suggest that people with schizophrenia have impaired GSH antioxidant capacity, alongside normal levels of key regulatory proteins.

scholarly journals Spatio-Temporal Differences in Dystrophin Dynamics at mRNA and Protein Levels Revealed by a Novel FlipTrap Line

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0128944 ◽  
Author(s):  
Frederique Ruf-Zamojski ◽  
Vikas Trivedi ◽  
Scott E. Fraser ◽  
Le A. Trinh
Keyword(s):  
Temporal Differences ◽  
Protein Levels ◽  
Spatio Temporal

Postnatal glucocorticoids induce α-ENaC formation and regulate glucocorticoid receptors in the preterm rabbit lung

2004 ◽  
Vol 286 (1) ◽  
pp. L73-L80 ◽  
Author(s):  
Shamimunisa B. Mustafa ◽  
Robert J. DiGeronimo ◽  
Jean A. Petershack ◽  
Joseph L. Alcorn ◽  
Steven R. Seidner
Keyword(s):  
Mrna Expression ◽  
Lung Tissue ◽  
Glucocorticoid Receptors ◽  
Fold Increase ◽  
Lung Epithelial Cells ◽  
Lung Water ◽  
Protein Levels ◽  
Tissue Weight ◽  
Postnatal Treatment ◽  
Distal Lung

At birth, lung fluid clearance is coupled to Na+ transport through epithelial Na+ channels (ENaC) in the distal lung epithelium. We evaluated the effect of postnatal glucocorticoids (GC) on lung α-ENaC expression in preterm 29-day gestational age (GA) fetal rabbits. Postnatal treatment of 29-day GA fetuses with 0.5 mg/kg of dexamethasone (Dex) iv resulted in a 2- and 22-fold increase in lung α-ENaC mRNA expression compared with saline-treated fetuses after 8 and 16 h, respectively. Lung α-ENaC protein levels in Dex-treated fetuses were also elevated compared with saline-treated counterparts. The extravascular lung water (EVLW)/dry lung tissue weight ratios of 29-day GA fetuses treated with either saline or Dex decreased over 24 h compared with that observed at birth; however, at 24 h, the EVLW/dry lung tissue weight ratios of saline- and Dex-treated fetuses were similar. Dex-induced α-ENaC mRNA and protein levels were attenuated by glucocorticoid receptor (GCR) antagonist RU-486 in fetal distal lung epithelial cells isolated from 29-day GA fetuses, indicating that GC-dependent augmentation of lung α-ENaC requires the presence of functional GCR. Lung GCR mRNA expression and protein levels were elevated in 29-day GA fetuses compared with fetuses at earlier GA. Exposure of 29-day GA fetuses to Dex for 16 h caused a 2.1-fold increase in lung GCR mRNA expression, but GCR protein levels were decreased in Dex-treated fetuses after 24 h. We conclude that postnatal treatment of preterm 29-day GA fetal rabbits with GC results in an elevation of lung α-ENaC accompanied by an autoregulation of pulmonary GCR.

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