Growth restriction in the rat alters expression of metabolic genes during postnatal cardiac development in a sex-specific manner

2013 ◽  
Vol 45 (3) ◽  
pp. 99-105 ◽  
Author(s):  
Glenn D. Wadley ◽  
Glenn K. McConell ◽  
Craig A. Goodman ◽  
Andrew L. Siebel ◽  
Kerryn T. Westcott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Transport ◽  
Mitochondrial Biogenesis ◽  
Cardiac Development ◽  
Growth Restriction ◽  
Antioxidant Defenses ◽  
Postnatal Life ◽  
Male And Female ◽  
Glut 1 ◽  
The Impact

This study investigated the impact of uteroplacental insufficiency and growth restriction on the expression of genes related to mitochondrial biogenesis, glucose transport, and antioxidant defenses in cardiac tissue at embryonic day 20 (E20) and postnatal days 1, 7, and 35 in male and female Wistar rats (8–10 per group). Bilateral uterine vessel ligation to induce growth restriction (Restricted) or sham surgery was performed at pregnancy day 18. In male and female Controls, expression of most cardiac genes decreased during postnatal life, including genes involved in mitochondrial biogenesis regulation such as PGC-1α, NRF-2, and mtTFA and the glucose transporter GLUT-1 ( P < 0.05). However, the pattern of gene expression during cardiac development differed in male and female Restricted rats compared with their respective Controls. These effects of restriction were observed at postnatal day 1, with female Restricted rats having delayed reductions in PGC-1α and GLUT-1, whereas males had exacerbated reductions in PGC-1α and mtTFA ( P < 0.05). By day 35, cardiac gene expression in Restricted hearts was similar to Controls, except for expression of the antioxidant enzyme MnSOD, which was significantly lower in both sexes. In summary, during postnatal life male and female Control rats have similar patterns of expression for genes involved in mitochondrial biogenesis and glucose transport. However, following uteroplacental insufficiency these gene expression patterns diverge in males and females during early postnatal life, with MnSOD gene expression reduced in later postnatal life.

scholarly journals Postnatal persistence of sex-dependent renal developmentally programmed structural and molecular changes in nonhuman primates

2020 ◽  
Author(s):  
Andrew C. Bishop ◽  
Kimberly D. Spradling-Reeves ◽  
Robert E. Shade ◽  
Kenneth J. Lange ◽  
Shifra Birnbaum ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Disease ◽  
Kidney Function ◽  
Nonhuman Primates ◽  
Disease Risk ◽  
Postnatal Life ◽  
Urine Metabolites ◽  
Baboon Model ◽  
Before And After ◽  
The Impact

AbstractBackgroundPoor nutrition during development programs kidney function. No studies on postnatal consequences of decreased perinatal nutrition exist in nonhuman primates (NHP) for translation to human renal disease. Our baboon model of moderate maternal nutrient restriction (MNR) produces intrauterine growth restricted (IUGR) and programs renal fetal phenotype. We hypothesized that the IUGR phenotype persists postnatally, influencing responses to a high-fat, high-carbohydrate, high-salt (HFCS) diet.MethodsPregnant baboons ate chow (Control; CON) or 70% of control intake (MNR) from 0.16 gestation through lactation. MNR offspring were IUGR at birth. At weaning, all offspring (CON and IUGR females and males, n=3/group) ate chow. At ~4.5 years of age, blood, urine, and kidney biopsies were collected before and after a 7-week HFCS diet challenge. Kidney function, unbiased kidney gene expression, and untargeted urine metabolomics were evaluated.ResultsIUGR female and male kidney transcriptome and urine metabolome differed from CON at 3.5 years, prior to HFCS. After the challenge, we observed sex-specific and fetal exposure-specific responses in urine creatinine, urine metabolites, and renal signaling pathways.ConclusionsWe previously showed mTOR signaling dysregulation in IUGR fetal kidneys. Before HFCS, gene expression analysis indicated that dysregulation persists postnatally in IUGR females. IUGR male offspring response to HFCS showed uncoordinated signaling pathway responses suggestive of proximal tubule injury. To our knowledge, this is the first study comparing CON and IUGR postnatal juvenile NHP and the impact of fetal and postnatal life caloric mismatch. Perinatal history needs to be taken into account when assessing renal disease risk.

Restriction of placental function alters heart development in the sheep fetus

2007 ◽  
Vol 293 (1) ◽  
pp. R306-R313 ◽  
Author(s):  
J. L. Morrison ◽  
K. J. Botting ◽  
J. L. Dyer ◽  
S. J. Williams ◽  
K. L. Thornburg ◽  
...  
Keyword(s):  
Heart Development ◽  
Relative Proportion ◽  
Relative Size ◽  
Neonatal Morbidity ◽  
Growth Restriction ◽  
Heart Weight ◽  
Postnatal Life ◽  
Fetal Sheep ◽  
The Impact

Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs, including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 control and 11 PR fetuses at 110–125 days of gestation (term: 150 ± 3 days). PR fetuses with a mean gestational Po2 < 17 mmHg were defined as hypoxic. At postmortem (<135 or >135 days), fetal hearts were collected, and cardiomyocytes were isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualize the nuclei, and the proportion of mononucleated cells and length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared with control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.

Stimulation of GLUT-1 glucose transporter expression in response to exposure to calcium ionophore A-23187

1995 ◽  
Vol 269 (5) ◽  
pp. C1228-C1234 ◽  
Author(s):  
Y. Mitani ◽  
A. Behrooz ◽  
G. R. Dubyak ◽  
F. Ismail-Beigi
Keyword(s):  
Gene Expression ◽  
Glucose Transport ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Calcium Ionophore ◽  
Tetraacetic Acid ◽  
Glut 1 ◽  
Mrna Induction ◽  
A 23187 ◽  
Mrna Content

We tested the hypothesis that an increase in cytosolic calcium concentration stimulates glucose transporter isoform (GLUT-1) gene expression. Exposure of a rat liver cell line (Clone 9) to 3 microM A-23187 for 12 h resulted in 3-, 5-, and 10-fold increases in cytochalasin B-inhibitable 3-O-methyl-D-glucose transport, GLUT-1 protein, and GLUT-1 mRNA content, respectively. The induction of GLUT-1 mRNA in response to A-23187 is not preceded by a significant decrease in cell ATP content. This induction is prevented by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in conjunction with ethylene glycol-bis(beta-aminoethyl ether)-N,N, N',N'-tetraacetic acid. To investigate the mechanism of GLUT-1 mRNA induction, we found that exposure to A-23187 stabilized GLUT-1 mRNA: with the employment of actinomycin D, GLUT-1 mRNA had a half-life of 1.5 and 5.5 h in control and A-23187-treated cells, respectively. In nuclear run-on assays, the rate of GLUT-1 gene transcription was stimulated 1.5- to 1.7-fold in nuclei isolated from cells exposed to A-23187 for either 30 min or 2 h. These results demonstrate that exposure to A-23187 stimulates GLUT-1 gene expression and that the increase in GLUT-1 mRNA content is mediated in part by enhanced GLUT-1 gene transcription as well as decreased GLUT-1 mRNA degradation. The increase in GLUT-1 mRNA content, in turn, is associated with increased cell GLUT-1 content and enhanced glucose transport.

Thyroid hormone increases the partitioning of glucose transporters to the plasma membrane in ARL 15 cells

1995 ◽  
Vol 269 (3) ◽  
pp. E605-E610
Author(s):  
R. S. Haber ◽  
C. M. Wilson ◽  
S. P. Weinstein ◽  
A. Pritsker ◽  
S. W. Cushman
Keyword(s):  
Gene Expression ◽  
Plasma Membrane ◽  
Cell Surface ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Transporter Gene ◽  
Glut 1 ◽  
Surface Partitioning ◽  
Enhanced Surface ◽  
Stimulation Of

The stimulation of glucose transport by 3,5,3'-triiodo-L-thyronine (T3) in the liver-derived ARL 15 cell line is only partly attributable to increased GLUT-1 glucose transporter gene expression. To test the hypothesis that T3 increases the partitioning of GLUT-1 to the cell surface, we quantitated surface GLUT-1 using the photolabel ATB-[3H]BMPA. In control cells only approximately 20% of total cellular GLUT-1 was present at the cell surface. T3 treatment (100 nM) for 6 h increased the rate of 2-deoxy-[3H]glucose (2-DG) uptake by 30, 92, and 95% in three experiments and increased surface GLUT-1 photolabeling by 17, 81, and 72%, respectively, with no increase in total cellular GLUT-1. T3 treatment for 48 h increased 2-DG uptake by 143, 172, and 216% in three experiments and increased cell surface GLUT-1 photolabeling by 88, 161, and 184%, respectively, with smaller increases in total cellular GLUT-1. T3 treatment for 48 h thus increased the fraction of cellular GLUT-1 at the plasma membrane from 21 +/- 2 to 35 +/- 3% (SE). We conclude that most of the early (6-h) stimulation of glucose transport by T3 in ARL 15 cells is mediated by an increase in the partitioning of GLUT-1 to the plasma membrane. With more chronic T3 treatment (48 h), the enhanced surface partitioning of GLUT-1 is persistent and is superimposed on an increase in total cellular GLUT-1, accounting for a further increase in glucose transport.

scholarly journals Impact of hot and cold exposure on human skeletal muscle gene expression

2017 ◽  
Vol 42 (3) ◽  
pp. 319-325 ◽  
Author(s):  
Roksana B. Zak ◽  
Robert J. Shute ◽  
Matthew W.S. Heesch ◽  
D. Taylor La Salle ◽  
Matthew P. Bubak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Room Temperature ◽  
Environmental Temperature ◽  
Human Model ◽  
Whole Body ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
The Impact

Many human diseases lead to a loss of skeletal muscle metabolic function and mass. Local and environmental temperature can modulate the exercise-stimulated response of several genes involved in mitochondrial biogenesis and skeletal muscle function in a human model. However, the impact of environmental temperature, independent of exercise, has not been addressed in a human model. Thus, the purpose of this study was to compare the effects of exposure to hot, cold, and room temperature conditions on skeletal muscle gene expression related to mitochondrial biogenesis and muscle mass. Recreationally trained male subjects (n = 12) had muscle biopsies taken from the vastus lateralis before and after 3 h of exposure to hot (33 °C), cold (7 °C), or room temperature (20 °C) conditions. Temperature had no effect on most of the genes related to mitochondrial biogenesis, myogenesis, or proteolysis (p > 0.05). Core temperature was significantly higher in hot and cold environments compared with room temperature (37.2 ± 0.1 °C, p = 0.001; 37.1 ± 0.1 °C, p = 0.013; 36.9 ± 0.1 °C, respectively). Whole-body oxygen consumption was also significantly higher in hot and cold compared with room temperature (0.38 ± 0.01 L·min−1, p < 0.001; 0.52 ± 0.03 L·min−1, p < 0.001; 0.35 ± 0.01 L·min−1, respectively). In conclusion, these data show that acute temperature exposure alone does not elicit significant changes in skeletal muscle gene expression. When considered in conjunction with previous research, exercise appears to be a necessary component to observe gene expression alterations between different environmental temperatures in humans.

scholarly journals TAMI-17. RELATIONSHIP BETWEEN IRON METABOLISM, IMMUNE CELL INFILTRATION AND SEX-BASED SURVIVAL DIFFERENCES IN GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii216-ii216
Author(s):  
Darya Nesterova ◽  
Sang Lee ◽  
Brad Zacharia ◽  
Elizabeth Proctor ◽  
Justin Lathia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Cell ◽  
Iron Regulation ◽  
Cell Infiltration ◽  
Low Grade ◽  
Immune Cell Infiltration ◽  
Male And Female ◽  
Mitochondrial Aconitase ◽  
Survival Differences ◽  
The Impact

Abstract Iron plays a central role in cellular metabolism, both in normal cellular functioning and in tumorigenesis. Recent evidence has shown sex-based survival differences in glioblastoma (GBM) may be related to differential expression of metabolism genes. We previously reported the iron regulating gene, HFE, was shown to have a sex-based survival impact in both low-grade gliomas and GBM. We additionally found that females with low HFE expressing tumors have significantly higher survival than males in GBM. To evaluate the relationship between iron gene expression and sex-based survival differences in GBM, we analyzed TCGA GBM gene expression and clinical data. We first analyzed the impact of iron genes on sex-based survival. In addition to HFE, FTL, TFRC, TF, and SLC39A8 (ZIP8), also showed sex-based survival differences. We then compared correlations of HFE and other iron genes to identify whether male and female GBMs differ in iron regulation and metabolism. HFE expression is significantly positively correlated with HMOX1, SLC25A28, SLC11A2, FTH1, HAMP, and TFR2 only in females. Alternatively, HFE expression is negatively correlated with ACO2 (mitochondrial aconitase) in males and ACO1 (cytoplasmic aconitase) in females. We noted that the expression of certain iron genes was highly associated with immune cell infiltration based on sex. TFR2, LRP1, and XIST expression were negatively correlated with low immune cell infiltration in females, but not males. Alternatively, in males, SLC11A2, ACO2, FOXO1, HIF1a, and HAMP genes were negatively correlated with immune infiltration. This suggests that differences in iron regulation between males and females may be contributing to differences in immune function and subsequent survival in GBM. These data suggest that the iron signature of a tumor reflects and possibly drives the metabolic and immune landscape of the tumor microenvironment thereby directly impacting survival differences between male and female GBMs.

Effects of Short and Prolonged Mild Intracellular Nitric Oxide Manipulations on Various Aspects of Insulin Secretion in INS-1E β-Cells

2012 ◽  
Vol 120 (04) ◽  
pp. 210-216 ◽  
Author(s):  
A. Natali ◽  
E. Santini ◽  
A. Delbarba ◽  
S. Baldi ◽  
E. Venturi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Insulin Secretion ◽  
Insulin Release ◽  
Mitochondrial Biogenesis ◽  
Culture Media ◽  
Short Exposure ◽  
Β Cells ◽  
Flat Dose ◽  
The Impact

AbstractWe aimed at evaluating the impact of short and prolonged mild manipulations of intracellular nitric oxide (NO) bioavailability on the main features of insulin secretion and whether NO promotes mitochondrial biogenesis in isolated β-cells.INS-1E β-cells were exposed to either the intracellular NO donor, hydroxylamine (HA), or the NO synthase inhibitor, L-nitro-arginine-methyl-ester (l-NAME), at concentrations lower than 2.0 mM. Glucose and arginine-induced insulin secretion (GIIS and AIIS) were measured after short (1 h) or prolonged (48 h) exposure to l-NAME 1.0 and 2.0 mM or HA 0.4 and 0.8 mM, lower concentrations were also evaluated for the 1 h effects. Basal insulin secretion (BIS), with either HA or l-NAME added to culture media, and peroxisome proliferators-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor-1 (NRF-1), and mitochondrial DNA transcription factor-A (Tfam) gene expression during chronic HA supplementation were also measured.Neither l-NAME nor HA affected insulin release at glucose 3.3 mM or in cell culture (BIS). Both short and prolonged cell exposure to l-NAME potentiated GIIS though with a flat dose-response curve while HA inhibited GIIS only at the highest concentration. AIIS was prevented by short exposure to l-NAME and potentiated by HA, while it did not respond to prolonged incubations. Prolonged cell exposure to HA had no effect on PGC-1α, NRF-1 or Tfam gene expression.In INS1E cells an intact NO synthesis is necessary to limit insulin release in response to acute glucose gradients and to fully respond to arginine while intracellular NO enrichment above the physiologic levels further inhibits GIIS and potentiate AIIS only when excessive. Prolonged NO manipulations do not affect AIIS, BIS or mitochondrial biogenesis.

scholarly journals Higher Hepatic miR-29 Expression in Undernourished Male Rats During the Postnatal Period Targets the Long-Term Repression of IGF-1

Endocrinology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 26-33 ◽  
Author(s):  
Gurjeev Sohi ◽  
Andrew Revesz ◽  
Julie Ramkumar ◽  
Daniel B. Hardy
Keyword(s):  
Gene Expression ◽  
Protein Restriction ◽  
Male Rats ◽  
Postnatal Life ◽  
Rat Offspring ◽  
The Metabolic Syndrome ◽  
Maternal Protein Restriction ◽  
Igf1 Expression ◽  
The Impact

Abstract A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepaticIgf1 expression, leading to impaired growth and metabolism. Previously, we have demonstrated that the timing of nutritional restoration in perinatal life can differentially program hepatic gene expression. Although microRNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3′ untranslated region of Igf1, we examined how protein restoration in maternal protein restriction rat offspring influences hepatic miR-29 and Igf1 expression in adulthood. Pregnant Wistar rats were designated into 1 of 4 dietary regimes: 20% protein (control), 8% protein during lactation only (LP-Lact), 8% protein during gestation only (LP1) or both (LP2). The steady-state expression of hepatic miR-29 mRNAsignificantly increased in LP2 offspring at postnatal day 21 and 130, and this was inversely related to hepatic Igf1 mRNA and body weight. Interestingly, this reciprocal association was stronger in LP-Lact offspring at postnatal day 21. Functional relevance of this in vivo relationship was evaluated by transfection of miR-29 mimics in neonatal Clone 9 rat hepatoma cells. Transfection with miR-29 suppressed Igf1 expression by 12 hours. Collectively, these findings implicate that nutritional restoration after weaning (post liver differentiation) in maternal protein restriction rat offspring fails to prevent long-term impaired growth, in part, due to miR-29 suppression of hepatic Igf1 expression. (Endocrinology 156: 3069–3076, 2015)

scholarly journals The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1022
Author(s):  
Edio Maldonado ◽  
Diego A. Rojas ◽  
Fabiola Urbina ◽  
Aldo Solari
Keyword(s):  
Gene Expression ◽  
Adjuvant Therapy ◽  
Chagas Disease ◽  
Latin American ◽  
Mitochondrial Biogenesis ◽  
Antioxidant Defenses ◽  
Myocardial Inflammation ◽  
Nuclear Respiratory Factor ◽  
Mitochondrial Functions ◽  
Activate Gene

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosome cruzi. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae family, although other transmission routes also exist. T. cruzi-infected cardiomyocytes at the chronic stage of the disease display severe mitochondrial dysfunction and high ROS production, leading to chronic myocardial inflammation and heart failure. Under cellular stress, cells usually can launch mitochondrial biogenesis in order to restore energy loss. Key players to begin mitochondrial biogenesis are the PGC-1 (PPARγ coactivator 1) family of transcriptional coactivators, which are activated in response to several stimuli, either by deacetylation or dephosphorylation, and in turn can serve as coactivators for the NRF (nuclear respiratory factor) family of transcription factors. The NRF family of transcriptional activators, namely NRF1 and NRF2, can activate gene expression of oxidative phosphorylation (OXPHOS) components, mitochondrial transcriptional factor (Tfam) and nuclear encoded mitochondrial proteins, leading to mitochondrial biogenesis. On the other hand, NRF2 can activate gene expression of antioxidant enzymes in response to antioxidants, oxidants, electrophile compounds, pharmaceutical and dietary compounds in a mechanism dependent on KEAP1 (Kelch-like ECH-associated protein 1). Since a definitive cure to treat Chagas disease has not been found yet; the use of antioxidants a co-adjuvant therapy has been proposed in an effort to improve mitochondrial functions, biogenesis, and the antioxidant defenses response. Those antioxidants could activate different pathways to begin mitochondrial biogenesis and/or cytoprotective antioxidant defenses. In this review we discuss the main mechanisms of mitochondrial biogenesis and the NRF2-KEAP1 activation pathway. We also reviewed the antioxidants used as co-adjuvant therapy to treat experimental Chagas disease and their action mechanisms and finish with the discussion of antioxidant therapy used in Chagas disease patients.

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