scholarly journals Protein O ‐GlcNAcylation levels are regulated independently of dietary intake in a tissue and time‐specific manner during rat postnatal development

2020 ◽  
Author(s):  
Thomas Dupas ◽  
Manon Denis ◽  
Justine Dontaine ◽  
Antoine Persello ◽  
Laurent Bultot ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Postnatal Development ◽  
Specific Manner ◽  
Time Specific

scholarly journals O-GlcNAc levels are regulated in a tissue and time specific manner during post-natal development, independently of dietary intake

2020 ◽  
Vol 12 (2-4) ◽  
pp. 221
Author(s):  
T. Dupas ◽  
M. Denis ◽  
J. Dontaine ◽  
A. Persello ◽  
L. Bultot ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Specific Manner ◽  
Time Specific

scholarly journals RelA/p65 Regulation of IκBβ

2005 ◽  
Vol 25 (12) ◽  
pp. 4956-4968 ◽  
Author(s):  
Erin Hertlein ◽  
Jingxin Wang ◽  
Katherine J. Ladner ◽  
Nadine Bakkar ◽  
Denis C. Guttridge
Keyword(s):  
Postnatal Development ◽  
26S Proteasome ◽  
Carboxyl Terminus ◽  
Growth Defect ◽  
Tight Control ◽  
Resistant Form ◽  
Specific Manner ◽  
Severe Growth Defect ◽  
Severe Growth ◽  
Hyperphosphorylated Form

ABSTRACT IκB inhibitor proteins are the primary regulators of NF-κB. In contrast to the defined regulatory interplay between NF-κB and IκBα, much less is known regarding the regulation of IκBβ by NF-κB. Here, we describe in detail the regulation of IκBβ by RelA/p65. Using p65 −/− fibroblasts, we show that IκBβ is profoundly reduced in these cells, but not in other NF-κB subunit knockouts. This regulation prevails during embryonic and postnatal development in a tissue-specific manner. Significantly, in both p65 −/− cells and tissues, IκBα is also reduced, but not nearly to the same extent as IκBβ, thus highlighting the degree to which IκBβ is dependent on p65. This dependence is based on the ability of p65 to stabilize IκBβ protein from the 26S proteasome, a process mediated in large part through the p65 carboxyl terminus. Furthermore, IκBβ was found to exist in both a basally phosphorylated and a hyperphosphorylated form. While the hyperphosphorylated form is less abundant, it is also more stable and less dependent on p65 and its carboxyl domain. Finally, we show that in p65 −/− fibroblasts, expression of a proteolysis-resistant form of IκBβ, but not IκBα, causes a severe growth defect associated with apoptosis. Based on these findings, we propose that tight control of IκBβ protein by p65 is necessary for the maintenance of cellular homeostasis.

Kisspeptin-Immunoreactivity Changes in a Sex- and Hypothalamic-Region-Specific Manner Across Rat Postnatal Development

2012 ◽  
Vol 24 (8) ◽  
pp. 1154-1165 ◽  
Author(s):  
E. Desroziers ◽  
J. D. Mikkelsen ◽  
A. Duittoz ◽  
I. Franceschini
Keyword(s):  
Postnatal Development ◽  
Hypothalamic Region ◽  
Specific Manner

scholarly journals Choline Supplementation in Obese Mouse Dams Alters Offspring DNA Methylation in a Time-Specific Manner

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 763-763
Author(s):  
Xinyin Jiang ◽  
Hunter Korsmo ◽  
Moshe Dembitzer ◽  
Sarah Khaldi ◽  
Shameera Sheeraz
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Maternal Obesity ◽  
Fetal Liver ◽  
Obese Mouse ◽  
Global Dna Methylation ◽  
Specific Manner ◽  
Time Specific ◽  
Visceral Adipose

Abstract Objectives Maternal obesity has long-term influence on metabolic health of offspring, partly through an epigenetic mechanism. Choline is a methyl donor which provides methyl groups for epigenetic modification such as DNA methylation. In this study, we examined the effect of maternal choline supplementation (MCS) on DNA methylation of offspring born to high-fat (HF) fed obese mouse dams. Methods C57BL/6J mice were fed either a 10% kcal normal fat (NF) or a 60% kcal HF diet with either 25 mM choline supplement or control drinking water from 4 weeks prior to mating until the end of gestation. The offspring were fed the HF diet for 6 weeks after weaning. We measured both global DNA methylation and site-specific methylation of several metabolic genes in the liver, visceral adipose tissue, and brain at both embryonic day E17.5 and after the post-weaning HF feeding. Results At E17.5, HF-MCS led to higher global DNA methylation in both fetal liver and brain. Methylation of one of the CpGs in the promoter region of Srebp1f (a gene that regulates lipogenesis) was also upregulated in the fetal liver by HF-MCS, accordingly there was lower expression of this gene (p < 0.05). However, HF-MCS had opposite effects on global DNA methylation after 6 weeks of post weaning HF feeding than during the fetal period. At this time point, HF-MCS led to hypomethylation of liver and visceral adipose tissue (p < 0.05). Global DNA methylation of the brain was decreased by post-weaning HF feeding but was not affected by maternal HF or MCS (p < 0.01). Conclusions In conclusion, MCS during maternal obesity in the perinatal period influences offspring DNA methylation in a time-specific manner. The epigenetic programming effect of MCS needs to be evaluated in both short and long term in the offspring. Funding Sources NIGMS.

Abstract 13917: O -GlcNAc Levels Are Regulated in a Time and Tissue Specific Manner Independently of Dietary Intake

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Thomas DUPAS ◽  
Manon DENIS ◽  
Justine Dontaine ◽  
Antoine Persello ◽  
Laurent Bultot ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Regulatory Mechanisms ◽  
Single Pair ◽  
Post Translational Modification ◽  
Western Blots ◽  
Tissue Specific ◽  
Regulatory Enzymes ◽  
Specific Manner ◽  
Before And After ◽  
Glcnac Transferase

Background: O -GlcNAcylation ( O -GlcNAc) is a post-translational modification involved in the stress response. A single pair of enzymes, O -GlcNAc transferase (OGT) and O -GlcNAcase (OGA) controls the O -GlcNAcylation. Due to the contribution of energy-linked metabolites (e.g. glucose, glutamine, etc.) to produce UDP-GlcNAc, the substrate used by OGT, O -GlcNAc is considered as a nutrient sensor. Metabolic sources vary from carbohydrates in utero , to fatty acids after birth then a mix once adult. Yet the link between diet composition and O -GlcNAc has never been explored. Purpose: Evaluate changes in O -GlcNAc levels and regulatory mechanisms throughout development. Methods: Organs were harvested from Wistar rats (n=6-8 for each group) before and after birth (D-1 and D0), in suckling animals (D12), after weaning with a standard (D28) or a carbohydrate free diet (D28F), and adult (D84). O -GlcNAc levels and regulatory enzymes were evaluated by Western blots. Mass spectrometry (MS) was performed to quantify known regulators of O -GlcNAc (n=6-8) and identify cardiac O -GlcNAcylated proteins at D0 and D28 (n=2). Results: O -GlcNAc levels fell after birth in the heart, brain and liver (2.5, 1.5 and 1.3-fold, respectively). Interestingly, while O -GlcNAc levels decrease progressively from D0 to D84 (5.75-fold p<0.05) in the heart, the O -GlcNAc changes are opposite and of much smaller magnitude in liver and brain. Regulatory mechanisms appear to be in accordance in heart with a decrease in OGT (4.5-fold; p<0.05), an increase in OGA (125-fold; p<0.05) expression and decrease in UDP-GlcNAc (3-fold; p<0.05) over time. Yet changes in expression of OGT, OGA and UDP-GlcNAc do not follow O -GlcNAc levels in brain and liver. O -GlcNAc levels are unaffected by weaning diet in any tissues. MS analyses identified changes in cardiac levels of specific O -GlcNAcylated proteins, namely those involved in the energy metabolism, such as ACAT1, which is only O -GlcNAcylated at D0. Conclusion: We demonstrate that O -GlcNAc levels are not linked to dietary intake and are regulated in a time and tissue-specific manner during postnatal development. We have identified by MS proteins with a particular O -GlcNAc signature across the development process suggesting specific role for those proteins.

scholarly journals Pregnancy-Associated Plasma Protein (PAPP)-A2 in Physiology and Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3576
Author(s):  
Vicente Barrios ◽  
Julie A. Chowen ◽  
Álvaro Martín-Rivada ◽  
Santiago Guerra-Cantera ◽  
Jesús Pozo ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Human Growth ◽  
Gene Encoding ◽  
Growth Physiology ◽  
Precise Control ◽  
Specific Manner ◽  
Igf Receptor ◽  
Time Specific ◽  
Shed Light ◽  
New Mutations

The growth hormone (GH)/insulin-like growth factor (IGF) axis plays fundamental roles during development, maturation, and aging. Members of this axis, composed of various ligands, receptors, and binding proteins, are regulated in a tissue- and time-specific manner that requires precise control that is not completely understood. Some of the most recent advances in understanding the implications of this axis in human growth are derived from the identifications of new mutations in the gene encoding the pregnancy-associated plasma protein PAPP-A2 protease that liberates IGFs from their carrier proteins in a selective manner to allow binding to the IGF receptor 1. The identification of three nonrelated families with mutations in the PAPP-A2 gene has shed light on how this protease affects human physiology. This review summarizes our understanding of the implications of PAPP-A2 in growth physiology, obtained from studies in genetically modified animal models and the PAPP-A2 deficient patients known to date.

scholarly journals Recent Advances in miRNA Delivery Systems

2021 ◽  
Vol 4 (1) ◽  
pp. 10
Author(s):  
Ishani Dasgupta ◽  
Anushila Chatterjee
Keyword(s):  
State Of The Art ◽  
Clinical Success ◽  
Delivery Systems ◽  
Regulatory Rna ◽  
Safe Delivery ◽  
Rna Molecules ◽  
Functional Studies ◽  
Current State ◽  
Specific Manner ◽  
Time Specific

MicroRNAs (miRNAs) represent a family of short non-coding regulatory RNA molecules that are produced in a tissue and time-specific manner to orchestrate gene expression post-transcription. MiRNAs hybridize to target mRNA(s) to induce translation repression or mRNA degradation. Functional studies have demonstrated that miRNAs are engaged in virtually every physiological process and, consequently, miRNA dysregulations have been linked to multiple human pathologies. Thus, miRNA mimics and anti-miRNAs that restore miRNA expression or downregulate aberrantly expressed miRNAs, respectively, are highly sought-after therapeutic strategies for effective manipulation of miRNA levels. In this regard, carrier vehicles that facilitate proficient and safe delivery of miRNA-based therapeutics are fundamental to the clinical success of these pharmaceuticals. Here, we highlight the strengths and weaknesses of current state-of-the-art viral and non-viral miRNA delivery systems and provide perspective on how these tools can be exploited to improve the outcomes of miRNA-based therapeutics.

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