CaR-mediated COX-2 expression in primary cultured mTAL cells

2001 ◽  
Vol 281 (4) ◽  
pp. F658-F664 ◽  
Author(s):  
Dairong Wang ◽  
Shao-Jian An ◽  
Wen-Hui Wang ◽  
John C. McGiff ◽  
Nicholas R. Ferreri
Keyword(s):  
Protein Expression ◽  
Intracellular Signaling ◽  
Primary Cultures ◽  
Extracellular Fluid ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Mrna Accumulation ◽  
Beneficial Effects ◽  
Cox 2 ◽  
Salt And Water Balance

Primary cultures of medullary thick ascending limb (mTAL) cells retain the capacity to express calcium-sensing receptor (CaR) mRNA and protein. Increases in cyclooxygenase-2 (COX-2) mRNA accumulation, protein expression, and PGE2 synthesis were observed in a dose- and time-dependent manner after exposure of these cells to extracellular calcium (Ca[Formula: see text]). Moreover, transfection of mTAL cells with a CaR overexpression vector significantly enhanced COX-2 expression and PGE2 production in response to calcium compared with cells transfected with an empty vector. Challenge with the CaR-selective agonist poly-l-arginine (PLA) also increased COX-2 mRNA accumulation, protein expression, and PGE2 synthesis. Furthermore, Ca[Formula: see text]- and PLA-mediated PGE2production was abolished in the presence of NS-398 or nimesulide, two different COX-2-selective inhibitors. These data suggest that intracellular signaling mechanisms initiated via activation of CaR contribute to COX-2-dependent PGE2 synthesis in the mTAL. Because Ca[Formula: see text] concentration varies along Henle's loop, calcium may contribute to salt and water balance via a COX-2- and CaR-dependent mechanism. Thus novel calcimimetics might be useful in conditions such as hypertension in which manipulation of extracellular fluid volume provides beneficial effects.

Calcium-Mediated Cox-2 Expression and Pge 2 Production in the Rat Medullary Thick Ascending Limb(mTAL) Is Tnf α -Dependent

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 709-709
Author(s):  
Dairong Wang ◽  
John C McGiff ◽  
Nicholas R Ferreri
Keyword(s):  
Protein Expression ◽  
Calcium Concentration ◽  
Primary Cultures ◽  
Extracellular Fluid ◽  
Cell Types ◽  
Thick Ascending Limb ◽  
Necrosis Factor Alpha ◽  
Severe Hypercalcemia ◽  
Cox 2

P89 Severe hypercalcemia often is associated with polyuria in patients. We have shown that mTAL cells express cyclooxygenase-2(COX-2) when challenged with tumor necrosis factor-alpha(TNF α ), an effect that was linked to the decrease in TNF α -mediated 86 Rb + uptake, an in vitro correlate of natriuresis. The mTAL expresses calcium sensing receptor(CaR), a G-protein coupled receptor that senses small changes in extracellular calcium concentration([Ca 2+ ] o ) and ultimately increases intracellular calcium concentration([Ca 2+ ] i ) and protein kinase C(PKC) activity. We assessed the effects of [Ca 2+ ] o on COX-2 and TNF α protein expression as calcium increases TNF α synthesis in certain cell types, and PMA, a PKC activator, induces COX-2 gene expression in mTAL cells. Western blot analysis showed that COX-2 protein expression was increased two-fold after challenge for 9 hours with 1.7 mM CaCl 2 . ELISA analysis revealed that PGE 2 formation was increased from 11 ± 1.5 to 68 ± 21 pg/μg protein (p<0.05) by 1.7 mM CaCl 2 ; no effect was observed when cells were exposed to 3.4 mM NaCl suggesting that the increase in PGE 2 synthesis was a function of increasing [Ca 2+ ] o . TNF α synthesis increased from 1.3 ± 0.1 to 5.4 ± 0.4 pg/μg protein (p<0.05) after challenge with 2 mM CaCl 2 . CaR agonist poly-L-arginine (100nM) increased PGE 2 production from 15 ± 0.1 to 66.3 ± 4.4 pg/μg protein (p<0.0001), and increased TNF α production from 0.7 ± 0.1 to 3.7 ± 0.3 pg/μg protein after a 9 hr incubation period. Pretreatment of cells with 1 μg/ml neutralizing TNF α antibody reduced COX-2 protein expression and PGE 2 production by approximately 40%. These data indicate that Ca 2+ o , as well as CaR selective agonists, increase mTAL COX-2 expression, PGE 2 formation, and TNF α production in primary cultures of mTAL cells. We conclude that the increases in COX-2 expression and PGE 2 production are, in part, TNF α -dependent, suggesting that Ca 2+ o may be a modulator of extracellular fluid volume regulation via a cytokine-mediated autocrine mechanism.

scholarly journals Differential regulation of NFAT5 by NKCC2 isoforms in medullary thick ascending limb (mTAL) cells

2011 ◽  
Vol 300 (4) ◽  
pp. F966-F975 ◽  
Author(s):  
Shoujin Hao ◽  
Hong Zhao ◽  
Zbigniew Darzynkiewicz ◽  
Sailaja Battula ◽  
Nicholas R. Ferreri
Keyword(s):  
Protein Expression ◽  
Laser Scanning ◽  
Transcriptional Activity ◽  
Primary Cultures ◽  
Fold Increase ◽  
Thick Ascending Limb ◽  
Activated T Cells ◽  
Mrna Accumulation ◽  
Medullary Thick Ascending Limb ◽  
Nacl Concentration

The effects of Na+-K+-2Cl− cotransporter type 2 (NKCC2) isoforms on the regulation of nuclear factor of activated T cells isoform 5 (NFAT5) were determined in mouse medullary thick ascending limb (mTAL) cells exposed to high NaCl concentration. Primary cultures of mTAL cells and freshly isolated mTAL tubules, both derived from the outer medulla (outer stripe>inner stripe), express NKCC2 isoforms A and F. The relative expression of NKCC2A mRNA was approximately twofold greater than NKCC2F in these preparations. The abundance of NKCC2A mRNA, but not NKCC2F mRNA, increased approximately twofold when mTAL cells were exposed for 2 h to a change in osmolality from 300 to 500 mosmol/kgH2O, produced with NaCl. Total NKCC2 protein expression also increased. Moreover, a 2.5-fold increase in NFAT5 mRNA accumulation was observed after cells were exposed to 500 mosmol/kgH2O for 4 h. Laser-scanning cytometry detected a twofold increase in endogenous NFAT5 protein expression in response to high NaCl concentration. Pretreatment with the loop diuretic bumetanide dramatically reduced transcriptional activity of the NFAT5-specific reporter construct TonE-Luc in mTAL cells exposed to high NaCl. Transient transfection of mTAL cells with shRNA vectors targeting NKCC2A prevented increases in NFAT5 mRNA abundance and protein expression and inhibited NFAT5 transcriptional activity in response to hypertonic stress. Silencing of NKCC2F mRNA did not affect NFAT5 mRNA accumulation but partially inhibited NFAT5 transcriptional activity. These findings suggest that NKCC2A and NKCC2F exhibit differential effects on NFAT5 expression and transcriptional activity in response to hypertonicity produced by high NaCl concentration.

Abstract 553: Prostaglandin E2 EP3 Receptor Downregulates COX2 Expression in the Medullary Thick Ascending Limb (mTAL) Induced by Hypertonic NaCl Intake

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Shoujin Hao ◽  
Carlos P Vio ◽  
Carlos Cespedes ◽  
Mariana Quiroz-Munoz ◽  
Nicholas R Ferreri
Keyword(s):  
Protein Expression ◽  
Tap Water ◽  
Receptor Expression ◽  
Free Access ◽  
Thick Ascending Limb ◽  
Mrna Levels ◽  
Mrna Accumulation ◽  
Cox 2 ◽  
Ep3 Receptor ◽  
In Cells

We recently showed that a novel negative feedback mechanism involving PGE 2 acting on EP3 receptors regulates cyclooxygenase-2 (COX-2) expression in the thick ascending limb (TAL) induced by the selective COX-2 inhibitors, celecoxib and rofecoxib. In the present study we tested the hypothesis that inhibition of EP3 facilitates COX-2 expression in the TAL induced by ingestion of hypertonic NaCl or exposure of mTAL cells to hypertonic media. COX-2 protein expression in the outer medulla (OM) increased 2.2±0.3 fold in mice given free access to 1% NaCl in the drinking water for 3 days compared with tap water; p<0.05. The increase was associated with a 4-fold elevation in COX-2 mRNA accumulation (tap water: 0.5±0.1 vs 1% NaCl: 1.9±0.4; p<0.05), and higher PGE 2 production by freshly isolated mTAL tubules (tap water: 87.6±9.4 vs 1% NaCl: 203.3±19.3 pg/mg protein; p<0.05). EP3 mRNA levels also increased approximately 2-fold in OM of mice ingesting 1% NaCl (tap water: 0.7±0.2 vs 1% NaCl: 1.3±0.2). Administration of a selective EP3 receptor antagonist (L-798106: 20μg/kg/day) for 2 days increased COX-2 mRNA accumulation in mTAL tubules (L-798106: 2.1±0.1 fold change vs control; p<0.05), and the elevation in COX-2 protein expression induced by 1% NaCl was increased an additional 50% in mice given L-798106. COX-2 mRNA accumulation in primary cultures of mTAL cells increased 2-fold in response to media made hypertonic by addition of NaCl (400 mosmol/kg H 2 O), compared with cells incubated in isotonic media. L-798106 increased COX-2 mRNA 2-fold in isotonic media and 4-fold in cells exposed to 400 mosmol/kg H 2 O. PGE 2 production by mTAL cells increased approximately 4-fold in response to challenge with 400 mosmol/kg H 2 O for 9 hr, and was inhibited in cells transiently transfected with a lentivirus shRNA construct (EGFP-C2-ex5) to silence COX-2 (286.1±14.8 to 64.3±5.2 pg/mg protein; p<0.05). Collectively, the data suggest that local hypertonicity in the mTAL is associated with an increase in COX-2 expression concomitant with elevated EP3 receptor expression, which attenuates COX-2 activity in this segment of the nephron. Moreover, PGE 2 signaling via EP3 receptors in the TAL may be part of a mechanism that regulates mTAL COX-2 expression and function in response to diverse stimuli.

Calcium-sensing receptor-mediated TNF production in medullary thick ascending limb cells

2002 ◽  
Vol 283 (5) ◽  
pp. F963-F970 ◽  
Author(s):  
Dairong Wang ◽  
Paulina L. Pedraza ◽  
Huda Ismail Abdullah ◽  
John C. McGiff ◽  
Nicholas R. Ferreri
Keyword(s):  
Protein Expression ◽  
Intracellular Signaling ◽  
Significant Inhibition ◽  
Thick Ascending Limb ◽  
Water Excretion ◽  
Medullary Thick Ascending Limb ◽  
Promoter Construct ◽  
Intracellular Ca ◽  
Cox 2 ◽  
Tnf Gene

Medullary thick ascending limb (mTAL) cells in primary culture express the Ca2+-sensing receptor (CaR), a G protein-coupled receptor that senses changes in extracellular Ca2+(Ca[Formula: see text]) concentration, resulting in increases of intracellular Ca2+concentration and PKC activity. Exposure of mTAL cells to either Ca[Formula: see text] or the CaR-selective agonist poly-l-arginine increased TNF-α synthesis. Moreover, the response to Ca[Formula: see text] was enhanced in mTAL cells transfected with a CaR overexpression vector. Transfection of mTAL cells with a TNF promoter construct revealed an increase in reporter gene activity after exposure of the cells to Ca[Formula: see text], suggesting that intracellular signaling pathways initiated by means of activation of a CaR contribute to TNF synthesis by a mechanism that involves transcription of the TNF gene. Neutralization of TNF activity with an anti-TNF antibody attenuated Ca2+-mediated increases in cyclooxygenase-2 (COX-2) protein expression and PGE2synthesis, suggesting that TNF exerts an autocrine effect in the mTAL, which contributes to COX-2-mediated PGE2production. Preincubation with the PKC inhibitor bisindolylmaleimide I inhibited Ca2+-mediated TNF production. Significant inhibition of COX-2 protein expression and PGE2synthesis also was observed when cells were challenged with Ca[Formula: see text] in the presence of bisindolylmaleimide I. The data suggest that increases in TNF production subsequent to activation of the CaR may be the basis of an important renal mechanism that regulates salt and water excretion.

scholarly journals Prostaglandin E2 EP3 receptor regulates cyclooxygenase-2 expression in the kidney

2012 ◽  
Vol 303 (3) ◽  
pp. F449-F457 ◽  
Author(s):  
Carlos P. Vio ◽  
Mariana Quiroz-Munoz ◽  
Catherina A. Cuevas ◽  
Carlos Cespedes ◽  
Nicholas R. Ferreri
Keyword(s):  
Protein Expression ◽  
Negative Feedback ◽  
Fold Increase ◽  
Treated Group ◽  
Cyclooxygenase 2 ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Mrna Accumulation ◽  
Cox 2 ◽  
Ep3 Receptor

Cyclooxygenase-2 (COX-2) is constitutively expressed and highly regulated in the thick ascending limb (TAL). As COX-2 inhibitors (Coxibs) increase COX-2 expression, we tested the hypothesis that a negative feedback mechanism involving PGE2 EP3 receptors regulates COX-2 expression in the TAL. Sprague-Dawley rats were treated with a Coxib [celecoxib (20 mg·kg−1·day−1) or rofecoxib (10 mg·kg−1·day−1)], with or without sulprostone (20 μg·kg−1·day−1). Sulprostone was given using two protocols, namely, previous to Coxib treatment (prevention effect; Sulp7-Coxib5 group) and 5 days after initiation of Coxib treatment (regression effect; Coxib10-Sulp5 group). Immunohistochemical and morphometric analysis revealed that the stained area for COX-2-positive TAL cells (μm2/field) increased in Coxib-treated rats (Sham: 412 ± 56.3, Coxib: 794 ± 153.3). The Coxib effect was inhibited when sulprostone was used in either the prevention (285 ± 56.9) or regression (345 ± 51.1) protocols. Western blot analysis revealed a 2.1 ± 0.3-fold increase in COX-2 protein expression in the Coxib-treated group, an effect abolished by sulprostone using either the prevention (1.2 ± 0.3-fold) or regression (0.6 ± 0.4-fold vs. control, P < 0.05) protocols. Similarly, the 6.4 ± 0.6-fold increase in COX-2 mRNA abundance induced by Coxibs ( P < 0.05) was inhibited by sulprostone; prevention: 0.9 ± 0.3-fold ( P < 0.05) and regression: 0.6 ± 0.1 ( P < 0.05). Administration of a selective EP3 receptor antagonist, L-798106, also increased the area for COX-2-stained cells, COX-2 mRNA accumulation, and protein expression in the TAL. Collectively, the data suggest that COX-2 levels are regulated by a novel negative feedback loop mediated by PGE2 acting on its EP3 receptor in the TAL.

scholarly journals Induction of Cyclooxygenase-2 in Thick Ascending Limb Cells by Adrenalectomy

2001 ◽  
Vol 12 (4) ◽  
pp. 649-658
Author(s):  
CARLOS P. VIO ◽  
SHAO-JIAN AN ◽  
CARLOS CÉSPEDES ◽  
JOHN C. MCGIFF ◽  
NICHOLAS R. FERRERI
Keyword(s):  
Protein Expression ◽  
Renal Tissue ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Thick Ascending Limb ◽  
Selective Marker ◽  
Mrna Accumulation ◽  
Cox 2 ◽  
Morphologic Analysis ◽  
Intact Rats

Abstract. Adrenalectomized (ADX) and sham-operated rats received either dexamethasone (DEX) or vehicle. Renal tissue was used for morphologic analysis, assessment of cyclooxygenase-2 (COX-2) protein expression and mRNA accumulation, and quantitation of COX-2 activity. In untreated or shamoperated rats, COX-2 protein was observed in a subset of tubular epithelial cells (<2%), which were located mainly in the cortex. All COX-2-positive cells also expressed Tamm-Horsfall glycoprotein, a highly selective marker for thick ascending limb (TAL) cells. After ADX, >30% of TAL cells expressed COX-2 in a manner consistent with recruitment of COX-2-positive TAL cells toward the medulla. Treatment of ADX rats with DEX reduced the number of COX-2-positive cells to that observed in sham-operated or intact rats. COX-2 mRNA accumulation was increased by ADX and partially attenuated by treatment with DEX. Western blot analysis of cortical microsomes revealed a substantial increase in COX-2 expression in ADX rats, compared with ADX/DEX-treated, sham-operated, or intact rats. The increase in COX-2 protein expression was associated with a twofold increase in prostaglandin E2 formation by cortical microsomes obtained from ADX rats, compared with sham-operated rats. It is concluded that ADX induces expression of enzymatically active COX-2, such that expression occurs in the cortical TAL and proceeds in a defined pattern toward the outer medullary TAL. It is suggested that ADX induces expression of TAL cells that, in the basal state, do not express COX-2 protein.

Tyrosine kinase inhibitors and antioxidants modulate NF-κB and NOS-II induction in retinal epithelial cells

1998 ◽  
Vol 275 (1) ◽  
pp. C208-C215 ◽  
Author(s):  
Violaine Faure ◽  
Yves Courtois ◽  
Olivier Goureau
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Nuclear Translocation ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner ◽  
Mrna Accumulation ◽  
Ifn Γ

Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-II) after activation with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Experiments were performed to investigate the effects of tyrosine kinase inhibitors (genistein and herbimycin A) and antioxidants [pyrrolidine dithiocarbamate (PDTC) and butyl hydroxyanisol] on NOS-II induction. The LPS-IFN-γ-induced nitrite release was inhibited in a concentration-dependent manner by these compounds. Analysis by Northern blot showed that this inhibitory effect correlated with a decrease in NOS-II mRNA accumulation. Analysis by electrophoretic mobility shift assay of the activation of the transcription factor nuclear factor-κB (NF-κB) involved in NOS-II induction demonstrated that LPS alone or combined with IFN-γ induced NF-κB binding. NF-κB activation was not changed by the presence of tyrosine kinase inhibitors but was totally prevented by PDTC pretreatment. Immunocytochemistry experiments confirmed the reduction of the nuclear translocation of NF-κB only by PDTC. Our results demonstrated the existence in retinal pigmented epithelial cells of different intracellular signaling pathways in NOS-II induction, since tyrosine kinase inhibitors blocked NOS-II mRNA accumulation without inhibiting NF-κB activation. Furthermore, the LPS-IFN-γ-induced NOS-II mRNA accumulation was sensitive to cycloheximide, suggesting that, in addition to NF-κB, transcriptional factors that require new protein synthesis are involved in NOS-II induction.

β-Adrenergic agonists stimulate Mg2+ uptake in mouse distal convoluted tubule cells

2000 ◽  
Vol 279 (6) ◽  
pp. F1116-F1123 ◽  
Author(s):  
Hyung Sub Kang ◽  
Dirk Kerstan ◽  
Long-Jun Dai ◽  
Gordon Ritchie ◽  
Gary A. Quamme
Keyword(s):  
Protein Kinase ◽  
Intracellular Signaling ◽  
Distal Tubule ◽  
Distal Convoluted Tubule ◽  
Maximal Response ◽  
Intracellular Camp ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Adrenergic Agonists ◽  
Concentration Dependent Manner

β-Adrenergic agonists influence electrolyte reabsorption in the proximal tubule, loop of Henle, and distal tubule. Although isoproterenol enhances magnesium absorption in the thick ascending limb, it is unclear what effect, if any, β-adrenergic agonists have on tubular magnesium handling. The effects of isoproterenol were studied in immortalized mouse distal convoluted tubule (MDCT) cells by measuring cellular cAMP formation with radioimmunoassays and Mg2+ uptake with fluorescence techniques. Intracellular free Mg2+ concentration ([Mg2+]i) was measured in single MDCT cells by using microfluorescence with mag-fura-2. To assess Mg2+uptake, MDCT cells were first Mg2+ depleted to 0.22 ± 0.01 mM by culturing in Mg2+-free media for 16 h and then placed in 1.5 mM MgCl2, and the changes in [Mg2+]i were determined. [Mg2+]i returned to basal levels, 0.53 ± 0.02 mM, with a mean refill rate, d([Mg2+]i)/d t, of 168 ± 11 nM/s. Isoproterenol stimulated Mg2+ entry in a concentration-dependent manner, with a maximal response of 252 ± 11 nM/s, at a concentration of 10−7 M, that represented a 50 ± 7% increase in uptake rate above control values. This was associated with a sixfold increase in intracellular cAMP generation. Isoproterenol-stimulated Mg2+ uptake was completely inhibited with RpcAMPS, a protein kinase A inhibitor, and U-73122, a phospholipase C inhibitor, and partially blocked by RO 31–822, a protein kinase C inhibitor. Accordingly, isoproterenol-mediated Mg2+ entry rates involve multiple intracellular signaling pathways. Aldosterone potentiated isoproterenol-stimulated Mg2+ uptake (326 ± 31 nM/s), whereas elevation of extracellular Ca2+ inhibited isoproterenol-mediated cAMP accumulation and Mg2+ uptake, 117 ± 37 nM/s. These studies demonstrate that isoproterenol stimulates Mg2+ uptake in a cell line of mouse distal convoluted tubules that is modulated by hormonal and extracellular influences.

NFAT regulates calcium-sensing receptor-mediated TNF production

2006 ◽  
Vol 290 (5) ◽  
pp. F1110-F1117 ◽  
Author(s):  
Huda Ismail Abdullah ◽  
Paulina L. Pedraza ◽  
Shoujin Hao ◽  
Karin D. Rodland ◽  
John C. McGiff ◽  
...  
Keyword(s):  
Extracellular Fluid ◽  
Dominant Negative ◽  
Peptide Ligand ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Calcium Sensing Receptor ◽  
Activated T Cells ◽  
Calcium Sensing ◽  
Dependent Activity ◽  
Calcineurin Activity

Because nuclear factor of activated T cells (NFAT) has been implicated in TNF production as well as osmoregulation and salt and water homeostasis, we addressed whether calcium-sensing receptor (CaR)-mediated TNF production in medullary thick ascending limb (mTAL) cells was NFAT dependent. TNF production in response to addition of extracellular Ca2+ (1.2 mM) was abolished in mTAL cells transiently transfected with a dominant-negative CaR construct (R796W) or pretreated with the phosphatidylinositol phospholipase C (PI-PLC) inhibitor U-73122. Cyclosporine A (CsA), an inhibitor of the serine/threonine phosphatase calcineurin, and a peptide ligand, VIVIT, that selectively inhibits calcineurin-NFAT signaling, also prevented CaR-mediated TNF production. Increases in calcineurin activity in cells challenged with Ca2+ were inhibited after pretreatment with U-73122 and CsA, suggesting that CaR activation increases calcineurin activity in a PI-PLC-dependent manner. Moreover, U-73122, CsA, and VIVIT inhibited CaR-dependent activity of an NFAT construct that drives expression of firefly luciferase in transiently transfected mTAL cells. Collectively, these data verify the role of calcineurin and NFAT in CaR-mediated TNF production by mTAL cells. Activation of the CaR also increased the binding of NFAT to a consensus oligonucleotide, an effect that was blocked by U-73122 and CsA, suggesting that a calcineurin- and NFAT-dependent pathway increases TNF production in mTAL cells. This mechanism likely regulates TNF gene transcription as U-73122, CsA, and VIVIT blocked CaR-dependent activity of a TNF promoter construct. Elucidating CaR-mediated signaling pathways that regulate TNF production in the mTAL will be crucial to understanding mechanisms that regulate extracellular fluid volume and salt balance.

scholarly journals Sex-Dependent Effects of Dietary Genistein on Echocardiographic Profile and Cardiac GLUT4 Signaling in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lana Leung ◽  
Joshua B. Martin ◽  
Todd Lawmaster ◽  
Kathryn Arthur ◽  
Tom L. Broderick ◽  
...  
Keyword(s):  
Protein Expression ◽  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Systolic Function ◽  
Intact Male ◽  
Male And Female ◽  
Beneficial Effects ◽  
Males And Females ◽  
Whole Heart ◽  
Fractional Shortening

This study aimed to determine whether genistein diet resulted in changes in cardiac function, using echocardiography, and expression of key proteins involved in glucose uptake by the myocardium. Intact male and female C57BL/6J mice (aged 4–6 weeks) were fed either 600 mg genistein/kg diet (600 G) or 0 mg genistein/kg diet (0 G) for 4 weeks. Echocardiography data revealed sex-dependent differences in the absence of genistein: compared to females, hearts from males exhibited increased systolic left ventricle internal dimension (LVIDs), producing a decrease in function, expressed as fractional shortening (FS). Genistein diet also induced echocardiographic changes in function: in female hearts, 600G induced a 1.5-fold (P<0.05) increase in LVIDs, resulting in a significant decrease in FS and whole heart surface area when compared to controls (fed 0 G). Genistein diet increased cardiac GLUT4 protein expression in both males (1.51-fold,P<0.05) and females (1.76-fold,P<0.05). However, no effects on the expression of notable intracellular signaling glucose uptake-regulated proteins were observed. Our data indicate that consumption of genistein diet for 4 weeks induces echocardiographic changes in indices of systolic function in females and has beneficial effects on cardiac GLUT4 protein expression in both males and females.

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