Increases in biliary cholesterol-to-bile acid ratio in pregnant hamsters fed low and high levels of cholesterol

2003 ◽  
Vol 284 (2) ◽  
pp. G263-G268 ◽  
Author(s):  
Lihang Yao ◽  
Paul A. Dawson ◽  
Laura A. Woollett
Keyword(s):  
Bile Acids ◽  
Stone Formation ◽  
Critical Role ◽  
Fold Increase ◽  
Late Gestation ◽  
Sterol Synthesis ◽  
Synthesis Rate ◽  
Hepatic Cholesterol Synthesis ◽  
Cholesterol Saturation ◽  
Acid Ratio

Gallstones develop when the secretion of cholesterol is elevated compared with the secretion of bile acids into bile. One of the risk factors for the formation of gallstones is pregnancy. Because the pregnancy-induced increase in hepatic cholesterol synthesis rates could play a critical role in the development of cholesterol stones, the aim of the present study was to determine whether stone formation, as assessed by the ratio of cholesterol to bile acids in bile, could be ablated by blocking the pregnancy-induced increase in hepatic sterol synthesis rates. Golden Syrian hamsters were fed either ground chow or chow supplemented with 0.5% cholesterol for 3 wk and studied in the nonpregnant state or in late gestation. In chow-fed animals, a 1.6-fold increase in the ratio of cholesterol to bile acids occurred simultaneously with a sevenfold increase in hepatic sterol synthesis rate and a ninefold increase in the amount of newly synthesized cholesterol secreted into the bile in late gestation. In the cholesterol-fed dams, an increase in the ratio of cholesterol to bile acids occurred even with the lack of induction of hepatic sterol synthesis rates during pregnancy. Thus it appears that the marked induction of hepatic sterol synthesis rates during gestation is not essential for the pregnancy-induced cholesterol saturation of bile when cholesterol is fed to animals.

Glucocorticoid regulation of epithelial sodium channel genes in human fetal lung

1997 ◽  
Vol 273 (1) ◽  
pp. L227-L233 ◽  
Author(s):  
V. C. Venkatesh ◽  
H. D. Katzberg
Keyword(s):  
Rna Polymerase Ii ◽  
Actinomycin D ◽  
Critical Role ◽  
Fetal Lung ◽  
Explant Culture ◽  
Late Gestation ◽  
Na Channel ◽  
Second Trimester ◽  
Cyclic Monophosphate ◽  
Human Fetal Lung

Pulmonary epithelial Na+ channels (ENaC), composed of three distinct subunits (alpha, beta, and gamma), play a critical role in the regulation of fluid reabsorption from airspaces of late-gestation fetal lung. We studied the expression of ENaC subunit genes in cultured human fetal lung. All three mRNAs were expressed at low levels in second trimester lung (13-32% of adult values at 24 wk gestation). There was a spontaneous increase of approximately threefold over preculture values of all three subunits within 24 h of explant culture in serum-free Waymouth's medium. Dexamethasone (Dex) induced all three mRNAs by two- to threefold. Maximal induction was noted by 8 h with 30-100 nM Dex and half-maximal stimulation with 3-10 nM Dex. Cycloheximide decreased basal expression of all three subunits by 8 h but did not alter the response to Dex. Actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), inhibitors of RNA polymerase II, decreased the basal and the Dex-induced expression of all three subunits with a more marked effect on human hENaC-gamma than on hENaC-alpha or hENaC-beta. Under conditions where transcription was blocked by actinomycin D or DRB, Dex did not alter the stability of the three mRNAs. Triiodothyronine (T3) at low (2 nM) or high (100 nM) concentrations had no effect on the expression of the three subunits in the presence or absence of low (10 nM) or high (100 nM) concentrations of Dex for 8 or 24 h. Similarly, 8-bromoadenosine 3',5'-cyclic monophosphate (2 microM) had no effect on basal or Dex-induced increase in the three subunits. We conclude that the three Na+ channel subunit genes are expressed in second trimester human fetal lung and are coordinately upregulated by glucocorticoid hormones but not by T3 or adenosine 3',5'-cyclic monophosphate. Glucocorticoid induction is receptor mediated, is primarily transcriptional, and does not require the induction of an intermediate protein for transcriptional enhancement. We speculate that induction of lung ENaC may contribute to the beneficial effects of antenatal glucocorticoids in premature babies.

scholarly journals Potential mechanisms involving the immobilization of Cd, As and Cr during swine manure composting

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hao-Nan Guo ◽  
Li-Xia Wang ◽  
Hong-Tao Liu
Keyword(s):  
Cation Exchange Capacity ◽  
Physicochemical Parameters ◽  
Redundancy Analysis ◽  
Critical Role ◽  
Swine Manure ◽  
Exchange Capacity ◽  
Bulking Agent ◽  
Initial Carbon ◽  
Acid Ratio ◽  
The Relationship

Abstract This study aims to investigate the relationship between key physicochemical parameters related to composting process and bioavailability of Cd, As and Cr during swine manure composting through regulating different initial carbon to nitrogen (C/N) ratios (15:1, 20:1, 25:1) and bulking agent types (straw, green waste). Results showed that higher initial C/N ratio of 20:1 or 25:1 and straw as bulking agent were optimal to reduce the bioavailability of Cd, As and Cr (62.4%, 20.6% and 32.2% reduction, respectively). Redundancy analysis implied that the bioavailability of Cd was significantly associated with total phosphorus and total nitrogen, deducing the formation of phosphate precipitation and biosorption might participated in the reaction process, while that of As and Cr were mainly influenced by organic matter (OM), cation exchange capacity (CEC) and OM, CEC, electric conductivity, respectively. A total of 48.5%, 64.6% and 62.2% of Cd, As and Cr redistribution information could be explained by the above parameters. Further correlation analysis revealed that bioavailable As and Cr were negatively correlated with humic acid to fulvic acid ratio. In summary, this study confirms that the mechanisms of phosphate precipitation, biosorption and humification played critical role in reducing Cd, As and Cr bioavailability during swine manure composting.

Molecular modulation of calcium oxalate crystallization

2006 ◽  
Vol 291 (6) ◽  
pp. F1123-F1132 ◽  
Author(s):  
James J. De Yoreo ◽  
S. Roger Qiu ◽  
John R. Hoyer
Keyword(s):  
Molecular Modeling ◽  
Calcium Oxalate ◽  
Stone Formation ◽  
Energy Levels ◽  
Critical Role ◽  
Specific Interactions ◽  
Crystal Surfaces ◽  
Site Specific

Calcium oxalate monohydrate (COM) is the primary constituent of the majority of renal stones. Osteopontin (OPN), an aspartic acid-rich urinary protein, and citrate, a much smaller molecule, are potent inhibitors of COM crystallization at levels present in normal urine. Current concepts of the role of site-specific interactions in crystallization derived from studies of biomineralization are reviewed to provide a context for understanding modulation of COM growth at a molecular level. Results from in situ atomic force microscopy (AFM) analyses of the effects of citrate and OPN on growth verified the critical role of site-specific interactions between these growth modulators and individual steps on COM crystal surfaces. Molecular modeling investigations of interactions of citrate with steps and faces on COM crystal surfaces provided links between the stereochemistry of interaction and the binding energy levels that underlie mechanisms of growth modification and changes in overall crystal morphology. The combination of in situ AFM and molecular modeling provides new knowledge that will aid rationale design of therapeutic agents for inhibition of stone formation.

Abstract 305: Tumor Necrosis Factor-α p75 Receptor, Satellite-Cell Survival, Activation and Muscle Regeneration

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
David A Goukassian ◽  
Tengiz Tkebuchava ◽  
Evelyn Bord ◽  
Marcy Silver ◽  
Cynthia Curry ◽  
...  
Keyword(s):  
Satellite Cells ◽  
Muscle Regeneration ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Fold Increase ◽  
Vegf Mrna ◽  
Gene Target ◽  
Ischemic Tissue ◽  
Tnf Α ◽  
P75 Receptor

Aging is a risk factor for ischemic diseases. TNF-α, a pro-inflammatory cytokine, is expressed in ischemic tissues and is known to modulate angiogenesis. Little is known about the role of TNF-α receptors (TNFR1/p55 and TNFR2/p75) in angiogenic signaling and muscle regeneration. We studied neovascularization in the hind limb ischemia (HLI) model in young and old TNFR2/p75 knockout (p75KO) and wild type (WT) age-matched controls. Between days 7–10 post-HL surgery 100% of old p75KOs experienced auto-amputation of the operated limbs, whereas none of the age-matched WT mice exhibited HL necrosis. Poor blood flow recovery in p75KOs was associated with decreased capillary density and significant reduction in the expression of VEGF mRNA transcripts in ischemic tissue. Compared to presurgery, on days 1–10 post-HL surgery there was 6–10-fold increase in the number of satellite-cells (embrionic NCAM staining) in WT mice, whereas in p75KOs after day 1 through day 10 satellite cells were not detecable. Indeed, p75KO tissue showed increased and prolonged (via day 10) inflammation - neutrophil (MPO-1) and macrophage (F/480) infiltration. Transplantation of WT/GFP (+) BM mononuclear cells into γ-irradiated p75KOs one month prior to HL surgery prevented limb loss, suggesting that ischemia-induced neovascularization and mobilization of BM-derived cells is mediated, at least in part, via TNFR2/p75 expressed in BM-derived cells. In the same BM transplantation model we evaluated the rate of proliferation (Ki67 + cells) of resident GFP (−) vs BM-derived GFP (+) cells. We found that in both WT and p75KO ischemic tissue Ki67 (+) cells almost exclusively were GFP (+), indicating that only BM-derived cells proliferate in the ischemic tissue. Interestingly, Ki67/GFP (+) cells started to appear in WT tissue by day 3 through day 21, whereas in p75KO tissue first proliferative activity was detected on day 28, suggesting extremely delayed recovery and regenaration in p75KO tissue. Our study suggests that, signaling through p75 receptor is required for collateral vessel development in ischemia-induced neovascularization as well as plays a critical role in muscle regeneration and suggest a potential gene target, which could be used to improve the repair of ischemic tissue in adults.

scholarly journals Effect of ursodeoxycholic acid on lipid metabolism: through the prism of evidence from 2019.

2020 ◽  
Vol 46 (1) ◽  
pp. 83-88
Author(s):  
N. B. Gubergrits ◽  
N.V. Byelyayeva ◽  
T. L. Mozhyna ◽  
G. M. Lukashevich ◽  
P. G. Fomenko
Keyword(s):  
Lipid Metabolism ◽  
Bile Acid ◽  
Bile Acids ◽  
De Novo ◽  
Gallstone Disease ◽  
Farnesoid X Receptor ◽  
Synthesis Rate ◽  
Primary Biliary Cholangitis ◽  
Fractional Synthesis Rate ◽  
Fractional Synthesis

After the discovery of the method of ursodeoxycholic acid’s (UDCA) synthesis and the publication of evidence confirming its ability to reduce the lithogenic properties of bile, active clinical use of UDCA began in the world. This drug, which has pleiotropic effect (choleretic, cytoprotective, immunomodulatory, antiapoptic, litholytic, hypocholesterolemic), has proven its effectiveness in the treatment various diseases: primary biliary cholangitis, intrahepatic cholestasis of pregnancy, gallstone disease. Being a tertiary bile acid, UDCA stimulates bile acid synthesis by reducing the circulating fibroblast growth factor 19 and inhibiting the activation of the farnesoid X-receptor (FXR), which leads to the induction of cholesterol-7α-hydroxylase, a key enzyme in the synthesis of bile acid de novo, mediating the conversion of cholesterol into bile acids. Changes in the formation of bile acids and cholesterol while taking UDCA intake is accompanied by activation of the main enzyme of cholesterol synthesis - 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under the influence of UDCA the activity of stearoyl-Coa desaturase (SCD) in visceral white adipose tissue increases. According to studies conducted in 2019, UDCA improves lipid metabolism by regulating the activity of the ACT/mTOR signaling pathway, reduces the synthesis of cholesterol, decreases the fractional synthesis rate of cholesterol and the fractional synthesis rate of triglycerides. It has been proved that UDCA is accompanied by a decrease in the level of total cholesterol and low density lipoprotein cholesterol.

scholarly journals Effect of inflammation-mediated endothelial metabolic shift on endothelial barrier function

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Aslam ◽  
H Idrees ◽  
C W Hamm ◽  
Y Ladilov
Keyword(s):  
Endothelial Cells ◽  
Glucose Uptake ◽  
Barrier Function ◽  
Atp Synthesis ◽  
Fold Increase ◽  
Endothelial Barrier ◽  
Synthesis Rate ◽  
Endothelial Barrier Function ◽  
Metabolic Switch ◽  
Barrier Integrity

Abstract Background The integrity of the endothelial cell barrier of the microvasculature is compromised by inflammation. The increased vascular permeability leads to tissue injury and organ dysfunction. In recent years, considerable advances have been made in the understanding of signalling mechanisms regulating the endothelial barrier integrity. The role of endothelial metabolism as a modulator of endothelial barrier integrity is not yet well-studied. The aim of the present study was to investigate the effect of inflammation on endothelial metabolism and its role in the maintenance of endothelial barrier integrity. Methods The study was carried out on cultured human umbilical vein endothelial cells and rat coronary microvascular endothelial cells. Inflammatory condition was simulated by treating cells with low concentrations (1 ng/mL) of TNFα for 24h. Endothelial barrier function was analysed by measuring the flux of albumen through endothelial monolayers cultured on filter membranes. Gene expression was analysed by qPCR-based assays. The capacity of endothelial cells for maximal ATP synthesis rate was investigated by the real-time live-cell imaging using FRET-based ATP-biosensor (live cell FRET). Total cellular ATP concentration was measured using luminescence-based commercial kit (ATPLite, PerkinElmer). Mitochondrial mass was analysed by the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA). The cellular glucose uptake was measured by fluorescent microscopy using a fluorescent analogue of glucose (2-NBDG). Results Treatment of human endothelial cells with TNFα resulted in significant suppression of mitochondrial and upregulation of glycolytic ATP synthesis rate, suggesting a metabolic switch. This was accompanied by a reduction in mitochondrial content (mtDNA/nDNA), reduction in total cellular ATP levels, an enhanced expression of glycolytic enzymes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK1), and enhanced glucose uptake by endothelial cells (n=5; p<0.05 for all parameters tested). Moreover, TNFα caused a 3-fold increase in endothelial permeability. Pharmacological inhibition of glycolysis either by partial replacement of glucose with 2-deoxy glucose (2DG) or an inhibition of PFKFB3 resulted in further worsening (a 5-fold increase in permeability) of TNFα-induced endothelial barrier failure. On the other hand pharmacological activation of AMPK, a potent inducer of mitochondrial biogenesis, could attenuate TNFα-induced but not 2DG-induced endothelial hyperpermeability. Conclusion The study demonstrates that TNFα induces metabolic switch towards glycolysis in endothelial cells. Moreover, the data suggest that upregulation of glycolysis may serve as an endogenous metabolic adaptation to the TNFα-induced suppression of mitochondrial ATP synthesis, which protects endothelial barrier integrity. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Justus-Liebig University GiessenDZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Bad Nauheim, Germany

scholarly journals Investigating the role of noncoding regulatory DNA in plasmid development for Yarrowia lipolytica

2020 ◽  
Author(s):  
Carmen Lopez ◽  
Mingfeng Cao ◽  
Zhanyi Yao ◽  
Zengyi Shao
Keyword(s):  
Yarrowia Lipolytica ◽  
Plasmid Stability ◽  
Critical Role ◽  
Fold Increase ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
Expression Platform ◽  
Regulatory Dna ◽  
Selection Of

Production of industrially relevant compounds in microbial cell factories can employ either genomes or plasmids as an expression platform. Selection of plasmids as pathway carriers is advantageous for rapid demonstration but poses a challenge of stability. Yarrowia lipolytica has attracted great attention in the past decade for the biosynthesis of chemicals related to fatty acids at titers attractive to industry, and many genetic tools have been developed to explore its oleaginous potential. Our recent studies on the autonomously replicating sequences (ARSs) of nonconventional yeasts revealed that the ARSs from Y. lipolytica showcase a unique structure that includes a previously unannotated sequence (spacer) linking the origin of replication (ORI) and the centromeric (CEN) element and plays a critical role in modulating plasmid behavior. Maintaining a native 645-bp spacer yielded a 4.5-fold increase in gene expression and higher plasmid stability compared to a more universally employed minimized ARS. Testing the modularity of the ARS sub-elements indicated that plasmid stability exhibits a pronounced cargo dependency. Instability caused both plasmid loss and intramolecular rearrangements. Altogether, our work clarifies the appropriate application of various ARSs for the scientific community and sheds light on a previously unexplored DNA element as a potential target for engineering Y. lipolytica.

scholarly journals Effect of insulin on the rates of synthesis and degradation of GLUT1 and GLUT4 glucose transporters in 3T3-L1 adipocytes

1993 ◽  
Vol 290 (3) ◽  
pp. 913-919 ◽  
Author(s):  
R J Sargeant ◽  
M R Pâquet
Keyword(s):  
Glucose Transporter ◽  
Insulin Treatment ◽  
Fold Increase ◽  
Glucose Transporters ◽  
Synthesis Rate ◽  
Insulin Stimulation ◽  
Transporter Proteins ◽  
Specific Manner ◽  
Glucose Transporter Proteins ◽  
Synthesis And Degradation

The effect of continuous insulin stimulation on the rates of turnover and on the total cellular contents of the glucose-transporter proteins GLUT1 and GLUT4 in 3T3-L1 adipocytes was investigated. Pulse-and-chase studies with [35S]methionine followed by immunoprecipitation of GLUT1 and GLUT4 with isoform-specific antibodies revealed the half-lives of these proteins to be 19 h and 50 h respectively. Inclusion of 100 nM insulin in the chase medium resulted in a decrease in the half-lives of both proteins to about 15.5 h. This effect of insulin was specific for the glucose-transporter proteins, as the average half-life of all proteins was found to be 55 h both with and without insulin stimulation. The effect of insulin on the rate of synthesis of the glucose transporters was determined by the rate of incorporation of [35S]methionine. After 24 h of insulin treatment, the rate of synthesis of GLUT1 and GLUT4 were elevated over control levels by 3.5-fold and 2-fold respectively. After 72 h of treatment under the same conditions, the rate of synthesis of GLUT1 remained elevated by 2.5-fold, whereas the GLUT4 synthesis rate was not different from control levels. Western-blot analysis of total cellular membranes revealed a 4.5-fold increase in total cellular GLUT1 content and a 50% decrease in total cellular GLUT4 after 72 h of insulin treatment. These observations suggest that the rates of synthesis and degradation of GLUT1 and GLUT4 in 3T3-L1 adipocytes are regulated independently and that these cells respond to prolonged insulin treatment by altering the metabolism of GLUT1 and GLUT4 proteins in a specific manner.

Abstract P430: VSMCs Increase Glutamine Utilization For Energy Metabolism During Obesity

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Krystal M Roggerson ◽  
Sharon Francis
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
High Fat Diet ◽  
Vascular Remodeling ◽  
Energy Demand ◽  
Critical Role ◽  
Fold Increase ◽  
Metabolic Reprogramming ◽  
High Fat ◽  
Low Fat

Obesity increases the risk of developing cardiovascular disease through vascular remodeling though the underlying mechanisms are not entirely understood. However, metabolic fuel partitioning and mitochondrial flexibility during energy metabolism may play a critical role. We demonstrated serum and glucocorticoid-inducible kinase 1 (SGK-1) is up-regulated in the vasculature of diet-induced obese mice and that SGK-1 deletion is protective against obesity-induced vascular remodeling by metabolically reprogramming vascular smooth muscle cell (VSMC) energy metabolism towards oxidative phosphorylation (OXPHOS) and away from glycolysis. Mitochondrial substrate availability and utilization of the primary metabolic fuels glucose, long chain fatty acids (LCFAs) and glutamine can drive metabolic reprogramming. Therefore, alterations in fuel utilization may contribute to vascular remodeling during obesity. The purpose of this study was to examine SGK-1’s role in 1) fuel dependency: a cell’s reliance for a specific fuel and 2) fuel capacity: a cell’s ability to oxidize a specific fuel to meet cellular energy demand under low-fat and high-fat diet-induced obesity. Using the MitoXpress Oxygen Consumption assay which measures OXPHOS, primary VSMCs isolated from wildtype (WT) and SMC-specific SGK-1 knockout (smSGK-1 KO) mice fed a 10% kcal low-fat or 45% kcal high-fat diet for eight weeks were seeded in a 96-well plate at a density of 6x10 4 cells/well in culture medium. To assess fuel dependency, cells were treated with fuel pathway inhibitors UK5099, Etomoxir or BPTES to block glucose, LCFA or glutamine oxidation, respectively. To measure fuel capacity, VSMCs were treated with a combination of two pathway inhibitors simultaneously. Next, samples were overlaid with a fluorescent extracellular oxygen consumption reagent, sealed with high-sensitivity mineral oil, then signals were read at 1.5-minute intervals for 2 hours at Ex/Em= 380/650 nm. Our results show WT VSMCs are exclusively glucose-dependent for OXPHOS regardless of dietary conditions. However, SGK-1 deletion induces a dependency for all three fuels for OXPHOS in VSMCs under low- and high-fat conditions. Even though WT and smSGK-1 KO VSMCs preferentially oxidized glucose for OXPHOS under low-fat conditions; SGK-1 deletion resulted in a 2.2-fold increase in glutamine capacity. Alternatively, WT VSMCs exposed to obesogenic conditions preferentially oxidized glutamine whereas SGK-1 deletion induced a nearly equal partitioning of all three fuels during obesity suggesting elevated mitochondrial flexibility. Overall, this study suggests SGK-1 increases glucose dependency for energy metabolism under physiological and obesogenic conditions. Also, increased glutamine utilization for OXPHOS during obesity may be an underlying cause of VSMC dysfunction and subsequent vascular impairment.

Abstract 3660: Cardioprotective Effect of Eicosapentaenoic Acid, an Important Fish Oil, through Suppression of Endothelin-1-induced Cardiomyocyte Hypertrophy via PPAR-α

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nobutake Shimojo ◽  
Subrina Jesmin ◽  
Masaaki Soma ◽  
Seiji Maeda ◽  
Takashi Miyauchi ◽  
...  
Keyword(s):  
Eicosapentaenoic Acid ◽  
Fish Oil ◽  
Fold Increase ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Pre Treatment ◽  
Cardiovascular Benefit ◽  
Hypertrophic Changes

A growing body of evidences report the cardiovascular benefit of fish oil including eicosapentaenoic acid (EPA) in humans and experimental animals. While many studies link EPA to cardiac protection, the effect of EPA on endothelin (ET)-1-induced cardiomyocyte hypertrophy is unknown. On the other hand, the previous study demonstrated peroxisomal proliferator-activated receptor (PPAR) -α ligand (fenofibrate) prevents ET-1-induced cardiomyocyte hypertrophy. Though EPA is one of the lignads of PPAR-α, there was no study linking relationship between EPA and PPAR-α on hypertrophied cadiomyocyte. The present study investigated whether ET-1-induced cardiomyocyte hypertrophy could be prevented by the pre-treatment of EPA. Cardiomyocytes were accumulated from neonatal rat heart, cultured and at day 4 of culture, the cardiomyocytes were divided into three groups: control, ET-1 (0.1nM) treated and EPA-pre-treated (10μM) ET-1 groups. A 90% increase in cardiomyocyte surface area, a 75% increase in protein synthesis rate and an elevated actinin expression in cardiomyocyte were observed after ET-1 administration and these changes were greatly prevented by EPA pre-treatment. ET-1-induced hypertrophied cardiomyocytes showed a 2.3-fold and 2.1-fold increase in ANP and BNP mRNA expression, respectively, which were also suppressed by EPA pre-treatment. Pre-treatment of EPA could also attenuate phosphorylated JNK (an important component of MAPK cascade), c-Jun and PPAR-α in ET-1-induced hypertrophied cardiomyocytes. In conclusion, the present study showed that ET-1 can induce significant hypertrophic changes in cardiomyocytes with upregulation of important hypertrophic markers, and that this remodeling was effectively prevented by the pre-administration of EPA through suppressing PPAR-α, phosporylated JNK, and c-Jun.

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