scholarly journals Gene-nutrient interactions during fetal development

Reproduction ◽  
2005 ◽  
Vol 130 (4) ◽  
pp. 401-410 ◽  
Author(s):  
Christopher A Maloney ◽  
William D Rees
Keyword(s):  
Gene Expression ◽  
Fetal Development ◽  
Mammalian Target Of Rapamycin ◽  
Eukaryotic Cells ◽  
Peroxisome Proliferator ◽  
Prenatal Programming ◽  
Adaptive Responses ◽  
Nutrient Interactions ◽  
Activator Proteins

Eukaryotic cells have evolved a complex series of nutrient sensors that protect them from damage caused by acute deficiencies and also mediate adaptive responses to prolonged excess or deficiency of particular nutrients. In adults gene expression is regulated by nutrients interacting with pathways involving mammalian target of rapamycin (mTOR), CCAAT/ enhancer-binding proteins (C/EBPs) and peroxisome proliferator activator proteins (PPARs). These systems are also present in key cells of the developing oocyte, embryo and fetus. In this review we will consider the role of interactions between genes and nutrients during reproduction with a particular emphasis on their possible involvement in the prenatal programming of glucose metabolism in the adult.

Roles of histone deacetylation and AMP kinase in regulation of cardiomyocyte PGC-1α gene expression in hypoxia

2013 ◽  
Vol 304 (11) ◽  
pp. C1064-C1072 ◽  
Author(s):  
Angela Ramjiawan ◽  
Rushita A. Bagchi ◽  
Alexandra Blant ◽  
Laura Albak ◽  
Maria A. Cavasin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylation ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Glucose Depletion ◽  
And Function ◽  
Amp Activated Protein Kinase

The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a key determinant of cardiac metabolic function by regulating genes governing fatty acid oxidation and mitochondrial biogenesis. PGC-1α expression is reduced in many cardiac diseases, and gene deletion of PGC-1α results in impaired cardiomyocyte metabolism and function. Reduced fuel supply generally induces PGC-1α expression, but the specific role of oxygen deprivation is unclear, and the mechanisms governing PGC-1α gene expression in these situations are poorly understood. During hypoxia of primary rat cardiomyocytes up to 12 h, we found that PGC-1α expression was downregulated via a histone deacetylation-dependent mechanism. Conversely, extended hypoxia to 24 h concomitant with glucose depletion upregulated PGC-1α expression via an AMP-activated protein kinase (AMPK)-mediated mechanism. Our previous work demonstrated that estrogen-related receptor-α (ERRα) regulates PGC-1α expression, and we show here that overexpression of ERRα was sufficient to attenuate PGC-1α downregulation in hypoxia. We confirmed that chronic hypoxia downregulated cardiac PGC-1α expression in a hypoxic but nonischemic hypobaric rat model of pulmonary hypertension. Our data demonstrate that depletion of oxygen or fuel results in repression or induction, respectively, of PGC-1α expression via discrete mechanisms, which may contribute to cardiac energetic derangement during hypoxia, ischemia, and failure.

scholarly journals BET Proteins Regulate Expression of Osr1 in Early Kidney Development

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1878
Author(s):  
Janina Schreiber ◽  
Nastassia Liaukouskaya ◽  
Lars Fuhrmann ◽  
Alexander-Thomas Hauser ◽  
Manfred Jung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cell ◽  
Kidney Development ◽  
Gene Activation ◽  
Renal Development ◽  
Prenatal Programming ◽  
Bet Inhibitor ◽  
Bet Inhibitors ◽  
Nephron Progenitor

In utero renal development is subject to maternal metabolic and environmental influences affecting long-term renal function and the risk of developing chronic kidney failure and cardiovascular disease. Epigenetic processes have been implicated in the orchestration of renal development and prenatal programming of nephron number. However, the role of many epigenetic modifiers for kidney development is still unclear. Bromodomain and extra-terminal domain (BET) proteins act as histone acetylation reader molecules and promote gene transcription. BET family members Brd2, Brd3 and Brd4 are expressed in the nephrogenic zone during kidney development. Here, the effect of the BET inhibitor JQ1 on renal development is evaluated. Inhibition of BET proteins via JQ1 leads to reduced growth of metanephric kidney cultures, loss of the nephron progenitor cell population, and premature and disturbed nephron differentiation. Gene expression of key nephron progenitor transcription factor Osr1 is downregulated after 24 h BET inhibition, while Lhx1 and Pax8 expression is increased. Mining of BRD4 ChIP-seq and gene expression data identify Osr1 as a key factor regulated by BRD4-controlled gene activation. Inhibition of BRD4 by BET inhibitor JQ1 leads to downregulation of Osr1, thereby causing a disturbance in the balance of nephron progenitor cell self-renewal and premature differentiation of the nephron, which ultimately leads to kidney hypoplasia and disturbed nephron development. This raises questions about the potential teratogenic effects of BET inhibitors for embryonic development. In summary, our work highlights the role of BET proteins for prenatal programming of nephrogenesis and identifies Osr1 as a potential target of BET proteins.

scholarly journals Role of the transcriptional factors FOXO1 and PPARG on gene expression of SLC2A4 in endometrial tissue from women with polycystic ovary syndrome

Reproduction ◽  
2010 ◽  
Vol 140 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Karla Kohan ◽  
Rodrigo Carvajal ◽  
Fernando Gabler ◽  
David Vantman ◽  
Carmen Romero ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Western Blot ◽  
Polycystic Ovary ◽  
Subcellular Location ◽  
Peroxisome Proliferator ◽  
Ovary Syndrome ◽  
Protein Levels ◽  
Gene And Protein Expression

Fifty to seventy percent of patients with polycystic ovary syndrome (PCOS) present hyperinsulinemia. On the other hand, reports indicate that forkhead box class O 1 (FOXO1) and peroxisome proliferator-activated receptor-γ (PPARG) are involved in the insulin signaling pathway, regulating the gene expression of SLC2A4 (GLUT4). The negative effect of FOXO1 over PPARG transcription disappears when FOXO1 is phosphorylated (p-FOXO1) and excluded from the nucleus, whereas PPARG can suppress gene expression of SLC2A4. Scarce knowledge is available in endometrium of women with PCOS and hyperinsulinemia (PCOSE h-Ins) about the role of these factors. We aimed to evaluate whether the endocrine and metabolic status of PCOS modify the levels of gene and protein expression of FOXO1, PPARG, and SLC2A4 in the endometria from hyperinsulinemic PCOS women compared with controls. In endometria from control (CE,n=7) or PCOSE h-Ins (n=7), we determined the subcellular location and protein levels of p-FOXO1Ser319 and FOXO1/FOXO4 by immunohistochemistry and western blot respectively; gene and/or protein levels of PPARG and SLC2A4 were evaluated by RT-PCR and/or western blot. Cytoplasm location for FOXO1 and p-FOXO1Ser319 was immunodetected in both groups of endometria, showing significantly higher staining in PCOSE h-Ins for these proteins (P<0.05). In PCOSE h-Ins, gene and protein levels of PPARG were significantly higher than in CE, whereasSLC2A4mRNA was decreased (P<0.05). In conclusion, the derepression of PPARG transcription by the high levels of p-FOXO1Ser319 could partially account for the lower levels of SLC2A4 found in PCOSE h-Ins, suggesting an alteration of the endometrial function in these patients.

Prenatal programming of obesity in a swine model of leptin resistance: modulatory effects of controlled postnatal nutrition and exercise

2014 ◽  
Vol 5 (3) ◽  
pp. 248-258 ◽  
Author(s):  
A. Barbero ◽  
S. Astiz ◽  
C. Ovilo ◽  
C. J. Lopez-Bote ◽  
M. L. Perez-Solana ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Muscle Growth ◽  
Leptin Resistance ◽  
Control Group ◽  
Swine Model ◽  
Main Role ◽  
Prenatal Programming ◽  
Prenatal Malnutrition

The main role of early nutritional programming in the current rise of obesity and associated diseases is well known. However, translational studies are mostly based in postnatal food excess and, thus, there is a paucity of information on the phenotype of individuals with prenatal deficiencies but adequate postnatal conditions. Thus, we assessed the effects of prenatal programming (comparing descendants from females fed with a diet fulfilling 100 or only 50% of their nutritional requirements for pregnancy) on gene expression, patterns of growth and fattening, metabolic status and puberty attainment of a swine model of obesity/leptin resistance with controlled postnatal nutrition and opportunity of exercise. Maternal restriction was related to changes in the relationships among gene expression of positive (insulin-like growth factors 1 and 2) and negative (myostatin) regulators of muscle growth, with negative correlations in gilts from restricted pregnancies and positive relationships in the control group. In spite of these differences, the patterns of growth and fattening and the metabolic features during juvenile growth were similar in control gilts and gilts from restricted pregnancies. Concomitantly, there was a lack of differences in the timing of puberty attainment. However, after reaching puberty and adulthood, females from restricted pregnancies were heavier and more corpulent than control gilts, though such increases in weight and size were not accompanied by increases in adiposity. In conclusion, in spite of changes in gene expression induced by developmental programming, the propensity for higher weight and adiposity of individuals exposed to prenatal malnutrition may be modulated by controlled food intake and opportunity of physical exercise during infant and juvenile development.

Mitochondria Are Fundamental for the Emergence of Metazoans: On Metabolism, Genomic Regulation, and the Birth of Complex Organisms

2020 ◽  
Vol 54 (1) ◽  
pp. 151-166 ◽  
Author(s):  
Hadar Medini ◽  
Tal Cohen ◽  
Dan Mishmar
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Genetic System ◽  
Eukaryotic Cell ◽  
Eukaryotic Cells ◽  
Intracellular Bacteria ◽  
Human Disorders ◽  
Genomic Regulation ◽  
Lines Of Evidence

Out of many intracellular bacteria, only the mitochondria and chloroplasts abandoned their independence billions of years ago and became endosymbionts within the host eukaryotic cell. Consequently, one cannot grow eukaryotic cells without their mitochondria, and the mitochondria cannot divide outside of the cell, thus reflecting interdependence. Here, we argue that such interdependence underlies the fundamental role of mitochondrial activities in the emergence of metazoans. Several lines of evidence support our hypothesis: ( a) Differentiation and embryogenesis rely on mitochondrial function; ( b) mitochondrial metabolites are primary precursors for epigenetic modifications (such as methyl and acetyl), which are critical for chromatin remodeling and gene expression, particularly during differentiation and embryogenesis; and ( c) mitonuclear coregulation adapted to accommodate both housekeeping and tissue-dependent metabolic needs. We discuss the evolution of the unique mitochondrial genetic system, mitochondrial metabolites, mitonuclear coregulation, and their critical roles in the emergence of metazoans and in human disorders.

scholarly journals Three distinct ribosome assemblies modulated by translation are the building blocks of polysomes

2015 ◽  
Vol 208 (5) ◽  
pp. 581-596 ◽  
Author(s):  
Gabriella Viero ◽  
Lorenzo Lunelli ◽  
Andrea Passerini ◽  
Paolo Bianchini ◽  
Robert J. Gilbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Building Blocks ◽  
Eukaryotic Cells ◽  
Central Control ◽  
Translational Activity ◽  
Control Layer

Translation is increasingly recognized as a central control layer of gene expression in eukaryotic cells. The overall organization of mRNA and ribosomes within polysomes, as well as the possible role of this organization in translation are poorly understood. Here we show that polysomes are primarily formed by three distinct classes of ribosome assemblies. We observe that these assemblies can be connected by naked RNA regions of the transcript. We show that the relative proportions of the three classes of ribosome assemblies reflect, and probably dictate, the level of translational activity. These results reveal the existence of recurrent supra-ribosomal building blocks forming polysomes and suggest the presence of unexplored translational controls embedded in the polysome structure.

scholarly journals The coordinate actions of calcineurin and Hog1 mediate the response to cellular stress through multiple nodes of the cell cycle network

2019 ◽  
Author(s):  
Cassandra M. Leech ◽  
Mackenzie J. Flynn ◽  
Heather E. Arsenault ◽  
Jianhong Ou ◽  
Haibo Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Regulatory Network ◽  
Adaptive Response ◽  
Environmental Stressors ◽  
Adaptive Responses ◽  
Cycle Arrest ◽  
Response To Stress ◽  
Stress Signals

SummaryUpon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between diverse stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the stress-activated phosphatase calcineurin (CN) in this process and show that CN utilizes multiple pathways to control the cell cycle. Upon activation, CN inhibits transcription factors (TFs) that regulate the G1/S transition through activation of the stress-activated MAPK Hog1. In contrast, CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner at multiple nodes of the cell cycle-regulatory network to rewire gene expression and arrest cells in response to stress. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors.

scholarly journals PPARα Gene Expression in the Developing Rat Kidney: Role of Glucocorticoids

2001 ◽  
Vol 12 (6) ◽  
pp. 1197-1203
Author(s):  
FATIMA DJOUADI ◽  
JEAN BASTIN
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Culture Media ◽  
Rat Kidney ◽  
Fold Increase ◽  
Kidney Cortex ◽  
Peroxisome Proliferator ◽  
Rat Kidney Cortex

Abstract. The α isoform of peroxisome proliferator-activated receptor (PPARα), which is highly expressed in the kidney, can stimulate the expression of genes that are involved in fatty acid catabolism and therefore might be involved in the control of renal fatty acid β-oxidation. PPARα expression and its regulation in the immature kidney are not well documented. This study delineated the developmental pattern of PPARα expression in the rat kidney cortex and the medulla between postnatal days 10 and 30 and investigated the role of glucocorticoids in regulating PPARα expression. In the cortex, PPARα mRNA and protein increased 2- and 1.8-fold, respectively, from 10 to 21 d and then decreased 1.5- and 2.4-fold from 21 to 30 d. In the medulla, PPARα mRNA and protein increased continuously 3.3- and 2.4-fold, respectively. It is shown here that acute treatment by dexamethasone of 10-d-old rats precociously induced a 4- to 6-fold increase in PPARα mRNA and a 1.8-fold increase in protein within 6 h in each part of the kidney. Chronic injection of dexamethasone for 3 d also increased PPARα mRNA 3.8- and 2.2-fold in the cortex and the medulla, respectively, with a 1.5- and 2-fold increase in protein. Furthermore, adrenalectomy prevented the increases in PPARα mRNA and protein in both the cortex and the medulla between postnatal days 16 and 21, and these could be restored by dexamethasone treatment. Finally, with the use of an established renal cell line, it was shown that glucocorticoids stimulate gene expression of PPARα and of medium chain acyl-CoA dehydrogenase (MCAD, a PPARα target gene) 2- to 4-fold and 1.5-fold, respectively, and that addition of fatty acids in the culture media led to a 2.2-fold increase in MCAD mRNA. Altogether, these results demonstrated that glucocorticoids are potent regulators of PPARα development in the immature kidney and that these hormones act in concert with fatty acids to regulate MCAD gene expression in renal cells.

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