scholarly journals Up-Regulation Mttp and Apob Gene Expression in Rat Liver is Related to Post-Lipectomy Hypertriglyceridemia

2015 ◽  
Vol 36 (5) ◽  
pp. 1767-1777 ◽  
Author(s):  
Agnieszka Dettlaff-Pokora ◽  
Tomasz Sledzinski ◽  
Julian Swierczynski

Background/Aims: The aim of this study was to explain the molecular basis for elevated concentrations of circulating triglycerides (TAGs) after partial surgical removal of adipose tissue (lipectomy) in rats. Methods: The levels of mRNA and protein: a) involved in synthesis of fatty acids and TAGs; b) participating in TAG-rich lipoproteins assembly and secretion; and c) transcription factors essential for maintaining TAG homeostasis were determined by RT-PCR and Western Blot in the livers of control and lipectomized rats. Results: Partial lipectomy was associated with increase: a) in serum and liver concentration of TAGs, and b) in the liver levels of mRNA of microsomal TAG transfer protein (MTP) and apolipoprotein B-100 (ApoB-100). These changes were tightly associated with up-regulation of Hnf1a and Hnf4a gene expression in the liver. Lipectomy was also reflected by a significant increase in the expression of genes encoding: a) fatty acid synthase (FASN), b) glycerol 3-phosphate acyltransferase 1 (GPAT1), diacylglycerol acyltransferases 1 and 2 (DGAT1 and DGAT2), c) spot 14 protein (S14) and SREBP-1 in the liver. Conclusion: Coordinated up-regulation of Mttp, Apob, Hnf1a, Hnf4a, Fasn, Gpam and Dgat (1 and 2) gene expressions may contribute to the increase in circulating and liver concentrations of TAGs after lipectomy in an experimental rat model.

2018 ◽  
Vol 17 (2) ◽  
pp. 41-46 ◽  
Author(s):  
S. G. Zakharov ◽  
A. K. Golenkov ◽  
A. V. Misyurin ◽  
E. V. Kataeva ◽  
A. A. Rudakova ◽  
...  

Introduction.The given data of fundamental studies of apoptosis processes in B-cell lymphocytic leukemia (B-CLL) testifies about the complexity and variety of mechanisms affecting the kinetics of normal cells and tumor lymphocytes in this disease. It is important to study the severity of clinical manifestations of the disease depending on the expression of the genes that modulate apoptosis.The purposeof the study is to compare the activity of genes encoding apoptosis modulators, the cell cycle and cancer-testicular PRAME protein with clinical manifestations of the disease in primary patients with B-CLL.Materials and methods.The level of expression of the proapoptotic genes FAS, TRAIL, TNFR2, DR4/5 and DR3, as well as the HSP27, XIAP genes, blocking apoptosis was determined in 23 patients with newly diagnosed chronic B-CLL. In addition, expression of genes TP53 and P21 and cancer-testis gene PRAME are tested.Results.According to the multivariate regression analysis, the FAS gene expression in the onset of the disease had the greatest impact on the clinical characteristics of the disease. In this connection, the patients were divided into groups with normal (group) and low gene level (group II). A low level of FAS expression (Me 387 %) was associated with stage II disease (p = 0.03), a large number of lympho cytes (p = 0.001), fewer erythrocytes (p = 0.08), and a lower level of TNFR2 gene expression (p = 0.08), high level of expression of XIAP, HSP27, P21. Overall, the anti-apoptotic potential in Group II patients was higher, which was accompanied by more pronounced clinical manifestations of the disease.Conclusions.The increased anti-apoptotic potential of tumor lymphocytes in newly diagnosed B-CLL is accompanied by a larger tumor mass and greater clinical and hematological manifestation of the disease.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ko-Ting Lu ◽  
Eric T Weatherford ◽  
Pimonrat Ketsawatsomkron ◽  
Justin L Grobe ◽  
Curt D Sigmund

Expression of the renin gene is required to maintain normal morphological and physiological identity of renal juxtaglomerular (JG) cells, yet the mechanisms regulating renin gene transcription remain elusive. We re-examined data from Brunskill et. al (JASN 22:2213, 2011), investigating genome-wide gene expression in JG and other renal cell types. Based on our previous data implicating nuclear receptors (RAR, RXR, VDR, PPARG, Nr2f2 and Nr2f6) in the regulation of mouse and human renin gene expression, we focused our analysis on the expression of genes encoding the 48 nuclear hormone receptors and their co-regulation with renin. Several nuclear receptors have an expression pattern emulating that of renin, that is, they were similarly enriched in JG cells but not in other cell types. These include Esr1, Nr1h4, Ppara, VDR, Nr1i2, Ppard, Hnf4g, Nr1h3, Thrb, Hnf4a, Esrrg, Nr4a3, Nr3c2, and Ar. We tested the hypothesis that a nuclear receptor that is co-regulated with renin may participate in renin gene regulation. To accomplish this, endogenous renin expression was evaluated in renin-expressing As4.1 cells after siRNA-mediated knock down of selected nuclear receptors. Each experiment included a negative control siRNA duplex (NC) that does not target any known genes. By way of example, siRNA-mediated inhibition of estrogen receptor alpha (Esr1) by 70-80% resulted in a 2-fold decrease in renin mRNA (fold change ± SEM: siEsr1: 0.4±0.2, p<0.001 vs NC). Similar results were obtained with a different siRNA targeting Esr1. Interestingly, loss of Esr1 also caused up-regulation of vitamin D receptor (VDR, 2.8±0.7 fold, p<0.001 vs NC) and Nr2f6 (2.0±0.2 fold, p<0.05 vs NC), both of which are known to be negative regulators of renin. Similarly, both renin (0.1±0.02, p<0.001 vs untreated) and Esr1 (0.3±0.1, p<0.05 vs untreated) mRNA were reduced in the kidney from mice treated with deoxycorticosterone acetate (50mg) and receiving 0.15 M NaCl in drinking water for 21 days (DOCA-salt). These data suggest Esr1 may regulate renin expression. Studies are in progress to assess if Esr1 stimulates renin expression on its own or acts by affecting the level of other nuclear receptors; and to determine if other co-regulated nuclear receptors also regulate expression of the renin gene.


2020 ◽  
Vol 105 (12) ◽  
pp. e4605-e4615
Author(s):  
Guido Di Dalmazi ◽  
Luca Morandi ◽  
Beatrice Rubin ◽  
Catia Pilon ◽  
Sofia Asioli ◽  
...  

Abstract Context DNA methylation has been identified among putative regulatory mechanisms for CYP11B2 expression in primary aldosteronism. Objective The objective of this work is to investigate DNA methylation and expression of genes encoding steroidogenic enzymes in benign adrenocortical tumors. Design and Setting This cross-sectional study took place at university hospitals. Patients We collected fresh-frozen tissues from patients with benign adrenocortical adenomas (n = 48) (nonfunctioning n = 9, autonomous cortisol secretion n = 9, Cushing syndrome n = 17, aldosterone-producing [APA] n = 13) and adrenal cortex adjacent to APA (n = 12). We collected formalin-fixed, paraffin-embedded (FFPE) specimens of paired APA and concurrent aldosterone-producing cell clusters (APCCs) (n = 6). Intervention DNA methylation levels were evaluated by quantitative bisulfite next-generation sequencing in fresh-frozen tissues (CYP11A1, CYP11B1, CYP11B2, CYP17A1, CYP21A2, HSD3B1, HSD3B2, NR5A1, STAR, and TSPO) and FFPE APA/APCC paired samples (CYP11B2). CYP11B1, CYP11B2, CYP17, CYP21, and STAR gene expressions were examined by quantitative real-time polymerase chain reaction. Main Outcome Measure The main outcome measure was DNA methylation. Results CYP11B2 methylation levels were significantly lower in APA than in other adrenal tissues (P &lt; .001). Methylation levels of the remaining genes were comparable among groups. Overall, CYP11B2 expression and DNA methylation were negatively correlated (ρ = –0.379; P = .003). In FFPE-paired APA/APCC samples, CYP11B2 methylation level was significantly lower in APA than in concurrent APCCs (P = .028). Conclusions DNA methylation plays a regulatory role for CYP11B2 expression and may contribute to aldosterone hypersecretion in APA. Lower CYP11B2 methylation levels in APA than in APCCs may suggest an APCC-to-APA switch via progressive CYP11B2 demethylation. Conversely, DNA methylation seems not to be relevant in regulating the expression of genes encoding steroidogenic enzymes other than CYP11B2.


2010 ◽  
Vol 104 (7) ◽  
pp. 941-950 ◽  
Author(s):  
Kenji Saito ◽  
Yutaka Ohta ◽  
Manabu Sami ◽  
Tomomasa Kanda ◽  
Hisanori Kato

Recent transcriptomics studies on the effect of long-term or severe energy restriction (ER) have revealed that many genes are dynamically modulated by this condition in rodents. The present study was conducted to define the global gene expression profile in response to mild ER treatment. Growing rats were fed with reduced amount of diet (5–30 % ER) for 1 week or 1 month. Using DNA microarray analysis of the liver, seventy-two genes that were consistently changed through the different ER levels were identified. Many were related to lipid metabolism including genes encoding key enzymes such as carnitine palmitoyltransferase 1 and fatty acid synthase. Interestingly, a number of genes were altered even by 5 % ER for 1 week where no differences in weight gain were observed. The information obtained in the present study can be used as a valuable reference data source in the transcriptomics studies of food and nutrition in which subtle differences in food intake sometimes hinder appropriate interpretation of the data.


2019 ◽  
Vol 53 (2) ◽  
pp. 71-82 ◽  
Author(s):  
Dmytro O. Minchenko

AbstractObjective. The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes through changes in the expression of numerous regulatory genes.Methods. The expression level of HLA-DRA, HLA-DRB1, HLA-G, HLA-F, and NFX1 genes as well as miR-190b was measured in the blood of obese adolescents without signs of resistance to insulin and with insulin resistance in comparison with the group of relative healthy control individuals without signs of obesity.Results. It was shown that obesity without signs of insulin resistance is associated with upregulation of the expression level of HLA-DRA and HLA-DRB1 genes, but with down-regulation of HLA-G gene expression in the blood as compared to control group of relative healthy adolescents. At the same time, no significant changes were observed in the expression level of HLA-F and NFX1 genes in the blood of this group of obese adolescents. Development of insulin resistance in obese individuals leads to significant down-regulation of HLA-DRA, HLA-DRB1, HLA-G, and HLA-F gene expressions as well as to up-regulation of NFX1 gene as well as microRNA miR-190b in the blood as compared to obese patients without signs of insulin resistance.Conclusions. Results of this study provide evidence that obesity affects the expression of the subset of genes related to immune response in the blood and that development of insulin resistance in obese adolescents is associated with strong down-regulation of the expressions of HLA-DRA, HLA-DRB1, HLA-F, and HLA-G genes, which may be contribute to the development of obesity complications. It is possible that transcription factor NFX1 and miR-190b participate in downregulation of HLA-DRA gene expression in the blood of obese adolescents with insulin resistance.


The study of phytochrome signalling has yielded a wealth of data describing both the perception of light by the receptor, and the terminal steps in phytochrome-regulated gene expression by a number of transcription factors. We are now focusing on establishing the intervening steps linking phytochrome photoactivation to gene expression, and the regulation and interactions of these signalling pathways. Recent work has utilized both a pharmacological approach in phototrophic soybean suspension cultures and microinjection techniques in tomato to establish three distinct phytochrome signal-transduction pathways: (i) a calcium-dependent pathway that regulates the expression of genes encoding the chlorophyll a/b binding protein ( CAB ) and other components of photosystem II; (ii) a cGMP-dependent pathway that regulates the expression of the gene encoding chalcone synthase ( CHS ) and the production of anthocyanin pigments; and (iii) a pathway dependent upon both calcium and cGMP that regulates the expression of genes encoding components of photosystem I and is necessary for the production of mature chloroplasts. To study the components and the regulation of phytochrome signal-transduction pathways, mutants with altered photomorphogenic responses have been isolated by a number of laboratories. However, with several possible exceptions, little real progress has been made towards the isolation of mutants in positive regulatory elements of the phytochrome signal-transduction pathway. We have characterized a novel phytochrome A (phyA)-mediated far-red light (FR) response in Arabidopsis seedlings which we are currently using to screen for specific phyA signal-transduction mutants.


1999 ◽  
Vol 19 (3) ◽  
pp. 2044-2050 ◽  
Author(s):  
Seok Hee Park ◽  
Sang Seok Koh ◽  
Jae Hwan Chun ◽  
Hye Jin Hwang ◽  
Hyen Sam Kang

ABSTRACT Expression of genes encoding starch-degrading enzymes is regulated by glucose repression in the yeast Saccharomyces cerevisiae. We have identified a transcriptional repressor, Nrg1, in a genetic screen designed to reveal negative factors involved in the expression of STA1, which encodes a glucoamylase. TheNRG1 gene encodes a 25-kDa C2H2zinc finger protein which specifically binds to two regions in the upstream activation sequence of the STA1 gene, as judged by gel retardation and DNase I footprinting analyses. Disruption of theNRG1 gene causes a fivefold increase in the level of theSTA1 transcript in the presence of glucose. The expression of NRG1 itself is inhibited in the absence of glucose. DNA-bound LexA-Nrg1 represses transcription of a target gene 10.7-fold in a glucose-dependent manner, and this repression is abolished in bothssn6 and tup1 mutants. Two-hybrid and glutathione S-transferase pull-down experiments show an interaction of Nrg1 with Ssn6 both in vivo and in vitro. These findings indicate that Nrg1 acts as a DNA-binding repressor and mediates glucose repression of the STA1 gene expression by recruiting the Ssn6-Tup1 complex.


Plant Disease ◽  
2017 ◽  
Vol 101 (9) ◽  
pp. 1606-1615 ◽  
Author(s):  
Zhen-Hua Cui ◽  
Wen-Lu Bi ◽  
Xin-Yi Hao ◽  
Peng-Min Li ◽  
Ying Duan ◽  
...  

Reddish-purple coloration on the leaf blades and downward rolling of leaf margins are typical symptoms of grapevine leafroll disease (GLD) in red-fruited grapevine cultivars. These typical symptoms are attributed to the expression of genes encoding enzymes for anthocyanins synthesis, and the accumulation of flavonoids in diseased leaves. Drought has been proven to accelerate development of GLD symptoms in virus-infected leaves of grapevine. However, it is not known how drought affects GLD expression nor how anthocyanin biosynthesis in virus-infected leaves is altered. The present study used HPLC to determine the types and levels of anthocyanins, and applied reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the expression of genes encoding enzymes for anthocyanin synthesis. Plantlets of Grapevine leafroll-associated virus 3 (GLRaV-3)-infected Vitis vinifera ‘Cabernet Sauvignon’ were grown in vitro under PEG-induced drought stress. HPLC found no anthocyanin-related peaks in the healthy plantlets with or without PEG-induced stress, while 11 peaks were detected in the infected plantlets with or without PEG-induced drought stress, but the peaks were significantly higher in infected drought-stressed plantlets. Increased accumulation of total anthocyanin compounds was related to the development of GLD symptoms in the infected plantlets under PEG stress. The highest level of up-regulated gene expression was found in GLRaV-3-infected leaves with PEG-induced drought stress. Analyses of variance and correlation of anthocyanin accumulation with related gene expression levels found that GLRaV-3-infection was the key factor in increased anthocyanin accumulation. This accumulation involved the up-regulation of two key genes, MYBA1 and UFGT, and their expression levels were further enhanced by drought stress.


2014 ◽  
Vol 54 (9) ◽  
pp. 1436 ◽  
Author(s):  
B. P. Dalrymple ◽  
B. Guo ◽  
G. H. Zhou ◽  
W. Zhang

Intramuscular fat content (IMF%) in cattle influences the value of individual animals, especially for higher marbling markets. IMF is triacylglyceride (TAG) in lipid droplets in the intramuscular adipocytes. However, there are many different pathways from feed intake to the final common process of TAG synthesis and storage as IMF. To evaluate the relative importance of different pathways we compared changes in the expression of genes encoding proteins involved in the TAG and fatty acid (FA) synthesis pathways in the longissimus muscle of Piedmontese × Hereford (P×H) and Wagyu × Hereford (W×H) crosses. Based on these changes we have estimated the relative contributions of FA synthesised de novo in the intramuscular adipocyte and the uptake of circulating FA (both free and from TAG), from the diet or synthesised de novo in other tissues, to TAG deposition as IMF. We have analysed the impact of different developmental times and different diets on these processes. Increased de novo FA synthesis in intramuscular adipocytes appeared to contribute more than increased FA uptake from circulation to the additional TAG deposition in W×H compared with P×H cattle between 12 and 25 months (forage diet). Changing diet from forage to concentrate appeared to increase the importance of FA uptake from circulation relative to de novo FA synthesis for TAG synthesis in intramuscular adipocytes. These results are consistent with the literature based on analysis of lipid composition. Gene expression appears to provide a simple assay for identification of the source of FA for the deposition of IMF.


Sign in / Sign up

Export Citation Format

Share Document