scholarly journals The Role of Beta-carotene Metabolism in Maternal Cardiac Remodeling: Findings in Mice Lacking Beta-carotene 9′,10′-oxygenase (BCO2) (FS06-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chelsee Holloway ◽  
You-Kyung Kim ◽  
Loredana Quadro
Keyword(s):  
Vitamin A ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Active Form ◽  
Beta Carotene ◽  
Regulatory Genes ◽  
Chow Diet ◽  
Mrna Levels ◽  
Β Carotene

Abstract Objectives High intake of fruits and vegetables, main vitamin A sources, is associated with improved cardiac function. β-carotene, the most abundant dietary precursor of vitamin A, is cleaved by β-carotene 15,15′-oxygenase (BCO1) and β-carotene 9′,10′-oxygenase (BCO2). However, BCO2 is the only β-carotene cleavage enzyme expressed in adult hearts. Cardiac mRNA levels of Bco2 are elevated at mid-gestation in wild-type (WT) mice when the heart is hypertrophic. In the absence of BCO2 (Bco2-/- mice) the maternal heart fails to enlarge. Therefore, we aim to elucidate the role of BCO2 in maternal cardiac hypertrophy and to determine if metabolic pathways in the heart are disrupted by loss of BCO2. We hypothesize that BCO2 contributes to maternal cardiac hypertrophy by affecting homeostasis of RA, the active form of vitamin A. Methods Age matched WT and Bco2-/- (KO) mice raised on a chow diet were sacrificed at 14.5 days pregnant. Cardiac mRNA and protein expression of retinoid and lipid regulatory genes were measured. HPLC and LC/MS detected cardiac retinoids (vitamin A and its derivatives) levels. Results Pregnancy (mid-gestation) is associated with cardiac RA deficiency in WT dams. KO mice already showed cardiac RA deficiency pre-pregnancy. KO female mice have reduced PDK4 mRNA expression and enhanced PDH activity (phosphorylation) in the heart, that is reversed earlier, at mid-gestation. KO mice have increased cardiac Glut1 mRNA expression and reduced triglyceride levels. Lipid regulatory genes such as Pgc1a and Scd1 are increased at mid-pregnancy in the heart of WT dams but not in KO mothers. Conclusions Our data indicates that RA may be involved in modulating the cardiac hypertrophy of pregnancy. Dysregulation of RA homeostasis in the heart of KO females results in metabolic adaptations that makes the heart of the non-pregnant females preferentially dependent on glucose as an energy source. During pregnancy retinoic deficiency in the KO heart may induce an earlier attenuation of PDH activity, facilitating utilization of fat over glucose as energy substrate. These and other findings support the hypothesis of a crucial role of BCO2 in regulating heart hypertrophy, at least in females. Funding Sources NIH/NHLBI F31.

DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics ◽  
2021 ◽  
Author(s):  
Beatriz Garcia-Ruiz ◽  
Manuel Castro de Moura ◽  
Gerard Muntané ◽  
Lourdes Martorell ◽  
Elena Bosch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Bipolar Disorder ◽  
Mrna Expression ◽  
Gene Expression Analysis ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Genome Wide ◽  
Isoform Expression

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results: DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion: DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

scholarly journals Analysis of βeta-carotene from Jongi (Dillenia Serrata Thunb.) as a source of vitamin A

2021 ◽  
Vol 10 (2) ◽  
pp. 184-190
Author(s):  
Khairun Nisa ◽  
Ryka Marina Walanda
Keyword(s):  
Chronic Disease ◽  
Vitamin A ◽  
Essential Role ◽  
Antioxidant Activities ◽  
Beta Carotene ◽  
Neurological Function ◽  
The Body ◽  
Yellow Orange ◽  
Β Carotene ◽  
Healthy Eyes

Beta-carotene is converted in the body to vitamin A, a powerful antioxidant that plays an essential role in maintaining healthy eyes, skin, and neurological function. Beta-carotene and other carotenoids have antioxidant activities and are valued for their ability to prevent chronic disease. β-carotene is found in yellow, orange, red, and green fruits. The purpose of this study was to determine the β-carotene in Jongi. Jongi (Dillenia Serrata Thunb.) is an endemic fruit of Sulawesi which contains β-carotene. The samples used in this study were raw jongi and ripe jongi extracted with n-hexane: acetone (1:4). To the samples were analyzed quantitatively using UV-Vis spectrophotometry at a wavelength of 450.00 nm. The results showed that the β-carotene in raw jongi was 0.3554 mg/100 g and the β- carotene in ripe jongi was 1.1841 mg/100 g. Ripe jongi consist of more β-carotene than the raw jongi, hence better as a source of Vitamin A.

scholarly journals Effectiveness of a Food-Based Intervention to Increase Breast Milk Vitamin A Content at One Month of Infancy

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 130-130
Author(s):  
Sumathi Swaminathan ◽  
Sumithra Selvam ◽  
Agnita Narendra ◽  
Tinku Thomas ◽  
Anil Vasudevan ◽  
...  
Keyword(s):  
Breast Milk ◽  
Vitamin A ◽  
Randomized Study ◽  
Beta Carotene ◽  
Maternal Blood ◽  
Energy Agency ◽  
Funding Sources ◽  
Deuterium Dilution ◽  
And Control ◽  
Β Carotene

Abstract Objectives Vitamin A requirements in early infancy are met only by breast milk intake. It is critical to ensure adequate breast milk vitamin A levels which also helps develop liver stores. The objective of the study was to evaluate the effect of a maternal food-based intervention on breast milk vitamin A content Methods Pregnant women (n = 50; 24 ± 1 week of gestation) were recruited for the randomized study. A 10 g of a green leafy vegetable powder (mint/coriander/curry) providing about 3200 μg β-carotene/day, for a period of 4 months up to 1 month of lactation were provided for intervention arm. Breast milk (BM) retinol concentration and BM volume were assessed. BM retinol and beta-carotene were assayed by HPLC and BM fat by creamatocrit method. BM retinol: fat ratio was calculated. The dose-to-mother deuterium dilution technique was used to estimate BM volume through enrichment of saliva measured by Fourier Transform Infrared Spectroscopy. Total BM retinol content was calculated from BM volume and the BM retinol (including beta-carotene:1 vitamin A RAE = 12 μg β-carotene). Inadequacy of intake was defined as proportion of infants with intake below a requirement of 400 μg RAE/day. Analysis of co-variance was performed after adjusting for age of mother, change in maternal blood retinol from baseline and BM fat, to compare outcomes between intervention and control arm. Results Maternal age, gestational age, socio-demographic characteristics and baseline vitamin A intake were comparable in both arms. Mean BM volume was similar in the 2 arms (676 ± 102 in intervention vs 630 ± 100 ml/day in control). BM retinol content (0.72 ± 0.12 vs 0.64 ± 0.11 μg/mL; P = 0.029) and BM retinol: fat ratio [0.41 (0.31, 0.47) vs 0.29 (0.21, 0.41), P = 0.011] were significantly higher in the intervention arm. The mean total BM retinol content was significantly higher in the intervention (482.2 ± 100.7 vs 406.5 ± 89.2 μg/day; P = 0.015; Cohen's effect size 0.80). Inadequacy of infant vitamin A intake was 14.3% in the intervention arm as against 39.1% in the control arm (P = 0.065). Conclusions The food-based intervention was effective in increasing vitamin A content in breast milk and thereby vitamin A intake in infants. Funding Sources International Atomic Energy Agency.

scholarly journals CMO1 Deficiency Abolishes Vitamin A Production from β-Carotene and Alters Lipid Metabolism in Mice

2007 ◽  
Vol 282 (46) ◽  
pp. 33553-33561 ◽  
Author(s):  
Susanne Hessel ◽  
Anne Eichinger ◽  
Andrea Isken ◽  
Jaume Amengual ◽  
Silke Hunzelmann ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Elevated Serum ◽  
Pcr Analysis ◽  
Marker Genes ◽  
Mouse Mutant ◽  
Adipose Tissues ◽  
Β Carotene

Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency in humans. These plant-derived compounds must be cleaved and metabolically converted by intrinsic carotenoid oxygenases to support the panoply of vitamin A-dependent physiological processes. Two different carotenoid-cleaving enzymes were identified in mammals, the classical carotenoid-15,15′-oxygenase (CMO1) and a putative carotenoid-9′,10′-oxygenase (CMO2). To analyze the role of CMO1 in mammalian physiology, here we disrupted the corresponding gene by targeted homologous recombination in mice. On a diet providing β-carotene as major vitamin A precursor, vitamin A levels fell dramatically in several tissues examined. Instead, this mouse mutant accumulated the provitamin in large quantities (e.g. as seen by an orange coloring of adipose tissues). Besides impairments in β-carotene metabolism, CMO1 deficiency more generally interfered with lipid homeostasis. Even on a vitamin A-sufficient chow, CMO1-/- mice developed a fatty liver and displayed altered serum lipid levels with elevated serum unesterified fatty acids. Additionally, this mouse mutant was more susceptible to high fat diet-induced impairments in fatty acid metabolism. Quantitative reverse transcription-PCR analysis revealed that the expression of peroxisome proliferator-activated receptor γ-regulated marker genes related to adipogenesis was elevated in visceral adipose tissues. Thus, our study identifies CMO1 as the key enzyme for vitamin A production and provides evidence for a role of carotenoids as more general regulators of lipid metabolism.

XIAP mRNA levels but not XAF1 or XIAP/XAF1 mRNA levels predict pathological response in bladder cancer patients treated with neoadjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20030-20030
Author(s):  
M. B. Pinho ◽  
J. Sellos ◽  
F. Costas ◽  
D. Herchenhorn ◽  
F. A. Peixoto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Pathological Response ◽  
Negative Regulator ◽  
Inhibitor Of Apoptosis ◽  
Mrna Levels ◽  
Bivariate Correlation ◽  
Xiap Expression

20030 Background: The relation between apoptosis-related molecules and chemosensitivity has been extensively studied. In recent years, attention has shifted to a new family of inhibitor of apoptosis proteins (IAPs). XIAP (X- linked inhibitor of apoptosis) is the most versatile and potent member of the IAP family. To date, the overexpression of XIAP has been detected in various cancers. XAF1 (X-linked inhibitor of apoptosis associated factor 1) is a new protein identified for its ability to interact with XIAP. Neither XIAP nor XAF1 or XIAP/XAF1 mRNA expression have been studied in bladder cancer patients. Methods: The expression of XIAP and XAF1 mRNA was analyzed by a real time quantitative fluorogenic PCR method in a group of 17 patients with locally advanced bladder cancer treated with a combination of neoadjuvant Gemcitabine and Cisplatin. The prognostic significance of XIAP and XAF1 mRNA expression and the correlation with several clinicopathological variables was evaluated. Results: XIAP and XAF1 mRNA expression was detected in all 17 (100%) case samples. The levels of XIAP mRNA expression showed a moderate variation among samples. In contrast, XAF1 and XIAP/XAF1 mRNA levels showed significant variation among samples. Bivariate correlation analyses revealed a significant positive Spearman direct correlation coefficient between the XIAP expression and the pathological response. No significant correlation was found for XAF1 expression as well as for the XIAP/XAF1 ratio and clinical and pathological response. Conclusions: This is first study to address the role of XIAP, its negative regulator XAF1, and the XIAP/XAF1 ratio in bladder cancer patients. The positive correlation between the XIAP mRNA expression and the pathological response is in line with a previous study from our group in which a correlation was found between XIAP expression and survival. All these observations point to a complex role of XIAP in tumor biology. XAF1 mRNA expression in bladder carcinomas did not achieve significance as an independent predictive and prognostic factor in a bivariate analysis. Further studies are necessary in order to better assess a possible clinical value for XIAP and XAF1 as predictive and prognostic markers in cancer patients. No significant financial relationships to disclose.

scholarly journals Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells.

1990 ◽  
Vol 171 (4) ◽  
pp. 1269-1281 ◽  
Author(s):  
M J Smyth ◽  
J R Ortaldo ◽  
Y Shinkai ◽  
H Yagita ◽  
M Nakata ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cytotoxic Lymphocytes ◽  
Mrna Levels ◽  
Cytotoxic Potential

Our studies have analyzed pore-forming protein (PFP) mRNA expression in resting and stimulated human peripheral blood CD3- large granular lymphocytes (LGL), CD3+ T cells, and their CD4+ or CD8+ subsets. Signals that stimulate T cells to develop cytotoxic activity (i.e., IL-2 or OKT-3 mAb) led to the induction of PFP mRNA in T cells. The data indicated that IL-2 directly increased PFP mRNA in the CD8+ subset of T cells, in the absence of new DNA or protein synthesis. Abrogation of IL-2-induced PFP mRNA expression and cytotoxic potential of T cells by the anti-p75 IL-2 receptor mAb suggested that low numbers of p75 IL-2 receptors on CD8+ T cells were capable of transducing signals responsible for these IL-2-induced effects. The induction of T cell PFP mRNA via CD3, using OKT-3 mAb, was less rapid but greater than that caused by IL-2; however, a combination of PMA and ionomycin, which bypasses crosslinking of the TCR/CD3 complex, could not mimic this increase in PFP mRNA levels in T cells. The role of second messenger systems in regulating PFP mRNA expression remains to be determined. In contrast, high constitutive PFP mRNA expression was observed in CD3- LGL and these mRNA levels could not be enhanced by stimulation with IL-2. The cytotoxic potential of peripheral blood T cells and LGL induced in response to IL-2 correlated with IL-2-induced PFP mRNA levels in these cells and was consistent with PFP being one of several important molecules involved in the effector function of cytotoxic lymphocytes.

scholarly journals A novel function of Tis11b/BRF1 as a regulator of Dll4 mRNA 3′-end processing

2011 ◽  
Vol 22 (19) ◽  
pp. 3625-3633 ◽  
Author(s):  
Agnès Desroches-Castan ◽  
Nadia Cherradi ◽  
Jean-Jacques Feige ◽  
Delphine Ciais
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Binding Site ◽  
Mammalian Cell ◽  
Mrna Stability ◽  
Untranslated Region ◽  
Vascular Network ◽  
Mrna Levels ◽  
Angiogenic Gene

Tis11b/BRF1 belongs to the tristetraprolin family, the members of which are involved in AU-rich-dependent regulation of mRNA stability/degradation. Mouse inactivation of the Tis11b gene has revealed disorganization of the vascular network and up-regulation of the proangiogenic factor VEGF. However, the VEGF deregulation alone cannot explain the phenotype of Tis11b knockouts. Therefore we investigated the role of Tis11b in expression of Dll4, another angiogenic gene for which haploinsufficiency is lethal. In this paper, we show that Tis11b silencing in endothelial cells leads to up-regulation of Dll4 protein and mRNA expressions, indicating that Dll4 is a physiological target of Tis11b. Tis11b protein binds to endogenous Dll4 mRNA, and represses mRNA expression without affecting its stability. In the Dll4 mRNA 3′ untranslated region, we identified one particular AUUUA motif embedded in a weak noncanonical polyadenylation (poly(A)) signal as the major Tis11b-binding site. Moreover, we observed that inhibition of Tis11b expression changes the ratio between mRNAs that are cleaved or read through at the poly(A) signal position, suggesting that Tis11b can interfere with mRNA cleavage and poly(A) efficiency. Last, we report that this Tis11b-mediated mechanism is used by endothelial cells under hypoxia for controlling Dll4 mRNA levels. This work constitutes the first description of a new function for Tis11b in mammalian cell mRNA 3′-end maturation.

scholarly journals Olanzapine inhibits hepatic apolipoprotein A5 secretion inducing hypertriglyceridemia in schizophrenia patients and mice

2021 ◽  
Author(s):  
Xiansheng Huang ◽  
Yiqi Zhang ◽  
Wenqiang Zhu ◽  
Piaopiao Huang ◽  
Jingmei Xiao ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Plasma Triglyceride ◽  
High Dose ◽  
Mrna Levels ◽  
Apolipoprotein A5 ◽  
Protein Levels ◽  
Olanzapine Treatment ◽  
Primary Mouse

Olanzapine, an antipsychotic drug, was reported to induce hypertriglyceridemia, whereas the underlying mechanism remains incompletely understood. This study was to determine the role of apolipoprotein A5 (apoA5) in olanzapine-induced hypertriglyceridemia. In this study, 36 drug-naive and first-episode schizophrenic adult patients (aged 18-60 years) in a multi-center clinical trial (ClinicalTrials.gov NCT03451734) were enrolled. Before and after olanzapine treatment, plasma lipid and apoA5 levels were detected. Moreover, 21 female C57BL/6 J mice (8 weeks old) were divided into 3 groups (n = 7/each group): low-dose olanzapine (3 mg/kg/day), high-dose olanzapine (6 mg/kg/day) and control group. After 6 weeks, plasma glucose, lipids and apoA5 as well as hepatic apoA5 protein and mRNA expression in these animals were detected. In our study in vitro, primary mouse hepatocytes and HepG2 cells were treated with olanzapine of 25, 50, 100 μmol/L, respectively. After 24 hours, apoA5 protein and mRNA levels in hepatocytes were detected. Our study showed that olanzapine treatment significantly increased plasma triglyceride levels and decreased plasma apoA5 levels in these schizophrenic patients. A significant negative correlation was indicated between plasma triglyceride and apoA5 levels in these patients. Consistently, olanzapine dose-dependently increased plasma triglyceride levels and decreased plasma apoA5 levels in mice. Surprisingly, an elevation of hepatic apoA5 protein levels was detected in mice after olanzapine treatment, with no changes of APOA5 mRNA expression. Likewise, olanzapine increased apoA5 protein levels in hepatocytes in vitro, without changes of hepatocyte APOA5 mRNA. Therefore, our study provides the first evidence about the role of apoA5 in olanzapine-induced hypertriglyceridemia. Furthermore, plasma apoA5 reduction, resulting in hypertriglyceridemia, could be attributed to olanzapine-induced inhibition of hepatic apoA5 secretion.

scholarly journals Exploration of Locally Grown Yellow and Green Pumpkin as a Potential Source of b-Carotene and Vitamin A

2020 ◽  
Vol 63 (3) ◽  
pp. 238-241
Author(s):  
Naseem Zahra ◽  
Alim-un- Nisa ◽  
Sajila Hina ◽  
Shahid Masood ◽  
Imran Kalim ◽  
...  
Keyword(s):  
Vitamin A ◽  
High Performance ◽  
Vitamin A Deficiency ◽  
Radical Scavenging Activity ◽  
Active Form ◽  
Radical Scavenging ◽  
Beta Carotene ◽  
The People ◽  
Anti Oxidant ◽  
Radical Content

Pumpkin is rich in beta-carotene which is used for preventing vitamin A deficiency. About 50 of carotenoids are the "Provitamin A compounds" which are precursors of retinol. Retinol is the active form of vitamin A. It plays an important role in vision. Beta carotene is an important anti-oxidant which protects the damaging of body cells by high free radical content because of its radical scavenging activity. The purpose of this study was to quantify the beta carotene and vitamin A present in yellow and green pumpkins. High performance liquid chromatography (HPLC) was used to analyze beta carotene and vitamin Yellow pumpkin contained the highest values of both the �-carotene and vitamin A than green pumpkin. The results illustrated that green pumpkin (Curcurbita pepo) possess 20.3µg/g beta carotene; 52.6µg/g vitamin A and yellow pumpkin (Curcurbita maxima) contains 35.7µg/g beta carotene and 60.2 µg/g vitamin A in their pulp. It was concluded that there is a need to promote the use of locally available sources of carotene and retinol to overcome nutrition deficiency in the people.

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