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1.
AIM：To investigate the different effects of ERK1/2/PPARα/SCAD (short-chain acyl-CoA dehydrogenase) signal pathways on the cardiac hypertrophy induced by insulin-like growth factors 1 (IGF-1) or phenylephrine (PE). METHODS：The neonatal rat cardiomyocytes induced by IGF-1 were used as the model of physiological cardiac hypertrophy, and those induced by PE were used as the model of pathological cardiac hypertrophy. The surface area of the cardiomyocytes, the expression of p-ERK1/2, PPARα and SCAD, the activity of SCAD and the content of free fatty acid in the cardiomyocytes were measured. RESULTS：Compared with the control cells, the surface area of the cardiomyocytes induced by IGF-1 and PE were both increased. Compared with the controls, the expression of SCAD and PPARα, and the activity of SCAD in the cardiomyocytes induced by IGF-1 were increased, while the expression of p-ERK1/2 was decreased. However, the cardiomyocytes treated with PE showed decreased expression of SCAD and PPARα, decreased activity of SCAD and increased expression of p-ERK1/2. Meanwhile, the decrease in free fatty acid in IGF-1-induced cardiomyocytes and the increase in PE-induced cardiomyocytes indicated that the fatty acid utilization was increased in the cardiomyocytes induced by IGF-1, but decreased in the cardiomyocytes induced by PE. CONCLUSION：The changes of p-ERK1/2, PPARα and SCAD in the cardiac hypertrophy induced by IGF-1 or PE indicate that the effects of ERK1/2/PPARα/SCAD signal pathways are different between physiological cardiac hypertrophy and pathological cardiac hypertrophy, and that SCAD may be a molecular marker of these 2 different cardiac hypertrophies and a potential therapeutic target for pathological cardiac hypertrophy.  相似文献   

2.
AIM：To investigate the effects of fenofibrate on angiotensin Ⅱ (AngⅡ)-induced cardiomyocyte hypertrophy. METHODS：Primary neonatal cardiomyocytes were pretreated with fenofibrate (10 μmol/L) for 1 h followed by stimulation with AngⅡ (100 nmol/L). The mRNA levels of ANF, BNP and β-MHC were measured by real-time PCR. Western blotting was employed to determine the nuclear translocations of NFATc4 and p65-NFκB. Co-immunoprecipitation was used to investigate the interaction of NFATc4 with p65-NFκB in the nucleus of cardiomyocytes. In addition, the DNA binding activity of NFATc4 on the BNP promoter was determined by EMSA. RESULTS：Fenofibrate significantly inhibited AngⅡ-induced cardiomyocyte hypertrophy. Fenofibrate treatment inhibited the nuclear translocations of NFATc4 and p65-NFκB, as well as the interactions of NFATc4 with p65-NFκB in the nucleus of cardiomyocytes induced by AngⅡ. Fenofibrate inhibited the binding activity of NFATc4 with the BNP promoter, which was strengthened by AngⅡ. CONCLUSION： Fenofibrate enhances the interaction of NFATc4 with PPARα, decreases the interaction of NFATc4 with p65-NFκB in the nucleus of cardiomyocytes, and inhibits the DNA binding activity of NFATc4 induced by AngⅡ, which may be the important mechanisms of fenofibrate on inhibiting cardiac hypertrophy.  相似文献   

3.
AIM: To investigate the change of short-chain acyl-CoA dehydrogenase(SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis.METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide(tBHP) were used as the model of cardiomyocyte apoptosis. The cell viability, the expression of SCAD at mRNA and protein levels, the activity of SCAD and the content of free fatty acids were determined.RESULTS: The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model. Compared with negative control group, SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes. Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP.CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis. Increase in the expression of SCAD may become an important part in intervening cardiomyocyte apoptosis.  相似文献   

4.
AIM: We hypothesize that peroxisome proliferator-activated receptor α(PPARα) agonists act directly on nitric oxide (NO) production in vascular endothelium. Thus, the purpose of this study is to investigate the effects of fenofibrate on endothelial NO synthase(eNOS) activity and its expression in cultured vascular endothelial cells. METHODS: Bovine aortic endothelial cells (BAECs) were treated with the PPARα activator fenofibrate. The eNOS activity and the expression of eNOS protein and its mRNA were determined. RESULTS: Our data show that fenofibrate increased eNOS activity in a dose-and time-dependent manner. At the concentration of 10 μmol/L or more, fenofibrate treatment caused a significant increase in eNOS activity. The maximal increase in eNOS activity(2.32±0.47 fold of the control) was observed with 50 μmol/L fenofibrate treatment for 48 h. Fenofibrate failed to increase eNOS activity at 1 and 12 h. RT-PCR analysis demonstrated that eNOS mRNA relative to β-actin mRNA significantly increased at concentrations of 5 μmol/L or more. It reached 2.08±0.33 fold of the control with 50 μmol/L fenofibrate. Significant increase in eNOS mRNA levels was observed after 6 h, and lasted for 48 h. The peak increase in eNOS mRNA levels(2.13±0.30 fold of the control,P<0.01) was observed with 50 μmol/L fenofibrate treatment for 12 h. Longer incubation of cells with 50 μmol/L fenofibrate caused no further increase. The treatment of BAECs with fenofibrate for 48 h demonstrated a concentration-dependent increase in eNOS protein levels as measured by Western blot analysis. Densitometric analysis indicated that there was a significant increase in eNOS to β-actin ratios after fenofibrate treatment at concentrations of 10,50 and 100 μmol/L(1.80±0.45, 2.70±0.42 and 2.20±0.32 fold of the control, respectively, P<0.01). The significant increase in eNOS protein levels was observed 12 h after treatment and lasted for 48 h. CONCLUSION: PPARα activator fenofibrate, enhances endothelial NO production by directly upregulating eNOS expression and activity.  相似文献   

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6.
AIM: To investigate the role of peroxisome proliferator-activated receptor β(PPARβ)-nitric oxide(NO) signal pathway in cardiomyocyte hypertrophy induced by high glucose(25.5 mmol/L) and insulin(0.1 μmol/L)(HGI). METHODS: The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by measuring the cell surface area, protein content, and the mRNA expression of atrial natriuretic factor(ANF). The mRNA and protein expression were measured by real-time PCR and Western blotting, respectively. The activity of NO synthase(NOS) and NO content were measured by a reagent kit through ultraviolet spectroscopy. RESULTS: HGI induced profound change of hypertrophic morphology, and significantly increased the cell surface area, protein content and mRNA expression of ANF(P<0.01), but decreased the expression of PPARβ at mRNA and protein levels(P<0.05). At the same time, the expression of inducible NOS(iNOS) was obviously elevated(P<0.01), which occurred in parallel with the rising NOS activity and NO concentration(P<0.01). GW0742(1 μmol/L), a selective PPARβ agonist, inhibited the cardiomyocyte hypertrophy induced by HGI(P<0.01), and up-regulated the expression of PPARβ at both mRNA and protein levels. Meanwhile, GW0742 also inhibited the increases in iNOS expression, NOS activity, and NO content induced by HGI, which were abolished by GSK0660(1 μmol/L), a selective PPARβ antagonist(P<0.01). CONCLUSION: PPARβ down-regulation and the following iNOS-NO activation are involved in the cardiomyocyte hypertrophy induced by HGI.  相似文献   

7.
AIM: To study the role of peroxisome proliferator-activated receptor-α (PPAR-α) signal transduction pathway in cardiac hypertrophy induced by high glucose and insulin (HGI). METHODS: The cultured neonatal rat cardiomyocytes were used to observe the effect of fenofibrate (FF), a selective PPAR-α agonist, on cardiomyocyte hypertrophy induced by HGI (glucose at concentration of 25.5 mmol/L and insulin at 0.1 μmol/L). The cardiomyocyte hypertrophic responses were assayed by measuring the cell surface area, protein content, and mRNA expression of atrial natriuretic factor (ANF). The expressions of mRNA and protein were assayed by real -time PCR and Western blotting. RESULTS: In cultured cardiomyocytes, HGI induced profound change of hypertrophic morphology, the significant increase in cell surface area, protein content and ANF mRNA expression compared to those in vehicle control (P<0.01), but the expressions of PPAR-α mRNA and protein decreased significantly (P<0.05). At the same time, the expression of cyclooxygenase 2 (COX-2), one of the PPAR-α downstream effectors was obviously elevated (P<0.05). However, FF (0.1, 0.3 and 1 μmol/L) inhibited the cardiomyocyte hypertrophy induced by HGI in a concentration-dependent manner (P<0.01). FF at concentration of 0.3 μmol/L increased the expressions of PPAR-α in both mRNA and protein levels (P<0.05) and inhibited the expressions of COX-2 (P<0.05), which were abolished by MK 886 (0.3 μmol/L), a selective PPAR-α antagonist (P<0.05). CONCLUSION: PPAR-α signal transduction pathway and its downstream effector COX-2 might involve in the cardiomyocyte hypertrophy induced by HGI.  相似文献   

8.
AIM: To investigate the effect of short-chain acyl-CoA dehydrogenase (SCAD) on collagen expression and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis. METHODS: The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was established. After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels, fatty acids beta oxidation rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined. RESULTS: The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells, and the expression of collagen I and collagen III was significantly upregulated. Compared with negative control group, SCAD expression and activity, fatty acid beta-oxidation rate and ATP significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts, and the expression of collagen I and collagen III was significantly up-regulated. CONCLUSION: The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD. SCAD may be a promising therapeutic target for myocardial fibrosis.  相似文献   

9.
AIM: To investigate the effect of macrophage peroxisome proliferator-activated receptor α (PPARα) activation on macrophage inflammation-induced activation and migration of cardiac fibroblasts. METHODS: Mouse bone marrow-derived macrophages were treated with vehicle, PPARα agonist WY14643 (10 μmol/L), angiotensin Ⅱ (Ang II; 1 μmol/L) or Ang II+WY14643 for 24 h, and the supernatants were collected as conditioned medium (CM) to stimulate cardiac fibroblasts for additional 24 h. The mRNA levels of PPARα, interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) in the macrophages as well as fibrotic markers collagen type Ⅰ alpha 2 chain (Col1a2), collagen alpha 1 chain (Col3a1) and actin alpha 2 (Acta2) in the cardiac fibroblasts were detected by RT-qPCR. The protein levels of IL-6 and IL-1β in the macrophages as well as collagen I, collagen III and α-smooth muscle actin (α-SMA; encoded by Acta2 gene) in the cardiac fibroblasts were determined by Western blot. Wound-healing assay was applied to eva-luate the migration ability of cardiac fibroblasts. RESULTS: Ang II significantly increased the mRNA levels of pro-inflammatory factors, such as IL-6, IL-1α and TNF-α, but decreased the mRNA level of PPARα in the macrophages. Administration of PPARα agonist WY14643 dramatically decreased Ang II-induced mRNA levels of IL-6, IL-1β and TNF-α in the macrophages, and significantly decreased Ang II-induced protein expression of IL-6 and pro-IL-1β in the macrophages. The CM from Ang II-treated macrophages significantly up-regulated the mRNA levels of Col1a2, Col3a1 and Acta2 in the cardiac fibroblasts, which were inhibited by the CM from WY14643-treated macrophages. The same results were observed in the protein levels of collagen I, collagen III and α-SMA in the cardiac fibroblasts. Moreover, the CM from Ang II-treated macrophages significantly promoted cardiac fibroblast migration, whereas the CM from WY14643-treated macrophages markedly inhibited macrophage inflammation-induced cardiac fibroblast migration. CONCLUSION: WY14643-activated PPARα inhibits activation and migration of cardiac fibroblasts by attenuating Ang II-induced macrophage inflammatory response.  相似文献   

10.
AIM: To investigate the differential expression of short-chain acyl-CoA dehydrogenase (SCAD) in cardiac hypertrophy induced by hypertension or exercise training. METHODS: Spontaneously hypertensive rats (SHR) were used as the model of pathological cardiac hypertrophy. The swim-trained rats were used as the model of physiological cardiac hypertrophy. The systolic pressure, cardiac hypertrophy parameters, echocardiogram parameters, free fatty acid in serum and cardiac muscle, and the expression and activity of SCAD in the left ventricle were measured. RESULTS: Compared with the control rats, trained rats developed an athletic heart, of which cardiac function was enhanced, whereas SHR developed hypertensive cardiac hypertrophy, of which cardiac function was deteriorated. Compared with the control rats, the ratios of left ventricular weight to body weight were both increased in trained rats and SHR, showing that the degrees of cardiac hypertrophy were similar in the 2 models. Compared with the control rats, the decrease of free fatty acid both in serum and myocardium indicated that the fatty acid utilization was increased in the left ventricle of trained rats. Meanwhile, the expression and activity of SCAD in the left ventricle of trained rats were increased. However, free fatty acid both in serum and myocardium were increased, indicating that the fatty acid utilization was decreased in the left ventricle of SHR. Furthermore, SHR had the decreased expression and activity of SCAD in the left ventricle. CONCLUSION: The changes of SCAD are different in cardiac hypertrophy induced by hypertension and exercise training, indicating that SCAD may be used as a molecular marker of physiological and pathological cardiac hypertrophy, and a potential therapeutic target of pathological cardiac hypertrophy.  相似文献   

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12.
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13.
AIM: To investigate the protective effect of quercetin on angiotensin Ⅱ (AngⅡ)-induced cardiomyocyte hypertrophy and its possible mechanism. METHODS: Cardiomyocyte hypertrophy was induced by AngⅡ (100 nmol/L) in primary neonatal cardiomyocytes and H9c2 cells. The cells were treated with different concentration of quercetin (10 μmol/L, 20 μmol/L and 40 μmol/L) for 48 h and then the cardiomyocyte surface areas were measured by immunofluorescence. Proteasome activity was detected by fluorescent peptide substrate. The phosphorylated levels of GSK-3α/β and Akt in H9c2 cells were determined by Western blot. RESULTS: Compared with control group, the cardiomyocyte surface areas were both increased in primary cultured neonatal cardiomyocytes and H9c2 cells, while the surface areas were significantly decreased by quercetin, especially at concentration of 20 μmol/L compared with Ang Ⅱ group (P<0.05). Compared with control group, the chymotrypsin-like, trypsin-like and caspase-like activities of proteasome were all increased in H9c2 cells (P<0.05). The trypsin-like and caspase-like activities of proteasome were inhibited by 20 μmol/L and 40 μmol/L quercetin, while chymotrypsin-like activity was inhibited only at 20 μmol/L of quercetin compared with Ang Ⅱ group (P<0.05). In addition, phosphorylated levels of GSK-3α-Ser21, GSK-3β-Ser9 and Akt-Ser473 in Ang Ⅱ group were all increased compared with control group, which were obviously inhibited by in 20 μmol/L and 40 μmol/L quercetin (P<0.05). CONCLUSION: Quercetin decreases cardiomyocyte hypertrophy through proteasome inhibition, which may be related to the inhibition of Akt and therefore increasing activation of GSK-3α/β in H9c2 cells.  相似文献   

14.
AIM: To investigate the expression of poly(ADP-ribose) polymerase-2 (PARP-2) during rat cardiac hypertrophy in vitro and in vivo, and to explore the effects of PARP-2 on the cardiac hypertrophy. METHODS: Abdominal aortic coarctation (AAC) was performed to establish a model of pressure overload-induced cardiac hypertrophy in SD rats. The expression of PARP-2 at mRNA and protein levels in the myocardium was determined by real-time PCR and Western blot. The hypertrophy model of the cardiomyocytes was induced by treating the cells with angiotensin Ⅱ (AngⅡ). PARP-2 was knocked down by siRNAs in neonatal rat cardiomyocytes and the cardiomyocyte hypertrophy was evaluated by measuring the mRNA levels of ANF, BNP, and β-MHC and the cellular surface area. RESULTS: The expression of PARP-2 at mRNA and protein levels was both increased in the AAC rats as compared with those in the sham animals. The expression of PARP-2 at mRNA and protein levels was also increased in a time- and concentration-dependent manner in AngⅡ-induced hypertrophy model of the cardiomyocytes. In the neonatal rat cardiomyocytes, knockdown of PARP-2 expression by siRNA attenuated AngⅡ-induced cardiac hypertrophy of the cardiomyocytes, indicating that endogenous PARP-2 played a positive regulatory role in cardiac hypertrophy. CONCLUSION: The mRNA and protein levels of PARP-2 increase in the in vitro and in vivo models of cardiac hypertrophy. Knockdown of PARP-2 protects cardiomyocytes from hypertrophy.  相似文献   

15.
AIM: To investigate the antihypertrophic function of adenosine monophosphate-activated protein kinase(AMPK) and its effects on myocardial fatty acid oxidation.METHODS: The model of cardiac hypertrophy was produced by banding abdominal aorta (transaortic constriction, TAC) in male Sprague-Dawley rats. 5-aminoimidazole-4-carboxamide ribonucleoside(AICAR), a pharmacological activator of AMPK, was injected subcutaneously (0.5 mg·kg-1·d-1) 24 hours after operation and continued till 7 weeks after operation. Echocardiographic and ventricular remodeling parameters, free fatty acid concentration in blood serum and myocardium, and expression of peroxisome proliferator-activated receptor(PPARα) and carnitine palmityl transferase(CPT-I) mRNA were investigated after treatment of AICAR or vehicle for 7 weeks. RESULTS: Compared with control group, treatment of rats subjected to TAC with AICAR significantly increased the mRNA expression of PPARα and CPT-I and subsequently decreased free fatty acid concentration in blood and myocardium, improved echocardiographic characteristics, and reduced the increases in the heart weight/body weight ratio and myocyte diameter.CONCLUSION: Pharmacological activation of AMPK may attenuate cardiac hypertrophy through increasing myocardial fatty acid oxidation.  相似文献   

16.
AIM: To study the effects of metoprolol (Meto) on the apoptosis of neonatal rat cardiomyocytes and the phosphorylation of connexin 43 (Cx43) induced by norepinephrine (NE). METHODS: Neonatal SD rat cardiomyocytes were divided into the following five groups (n=6 in each group): (1) control (Con) group: no treatment; (2) NE group: treatment with NE at 0.1 μmol/L for 24 h; (3) NE+Meto group: simultaneous treatment with NE and Meto both at 01 μmol/L for 24 h; (4) NE+Meto+PD98059 group: pretreatment with extracellular signal-regulated kinase (ERK) phosphorylation inhibitor PD98059 at 10 μmol/L for 30 min and then treatment with NE and Meto both at 01 μmol/L for 24 h; (5) NE+PD98059 group: pretreatment with PD98059 at 10 μmol/L for 30 min and then treatment with NE at 01 μmol/L for 24 h. The beating rates of cardiomyocytes in various groups were calculated, and the viability of cardiomyocytes was assayed by MTT method. The Cx43 mRNA expression was detected by RT-PCR, and the protein expression of phosphorylated Cx43 (p-Cx43), phosphorylated ERK1/2 (p-ERK1/2) and cleaved caspase-3 was detected by Western blotting. RESULTS: (1) Separate NE treatment could significantly increased the beating rate of cardiomyocytes and reduced cell viability, while Meto showed the opposite effects. PD98059 treatment had no significant effect on cardiomyocyte beating rate, but suppressed Meto to improve cell viability to some extent. (2) Compared with Con group, separate NE treatment significantly increased the Cx43 mRNA expression (P<001). Compared with NE group, Meto or PD98059 intervention could significantly inhibited Cx43 mRNA expression (both P<001), and simultaneous treatment with Meto and PD98059 could further suppress Cx43 mRNA expression up-regulated by NE (P<001). (3) Compared with NE group, Meto significantly inhibited the increased p-Cx43, p-ERK1/2 and cleaved caspase-3 expression induced by NE (P<001), and simultaneous treatment with Meto and PD98059 could further enhance the inhibition of p-Cx43, p-ERK1/2 and cleaved caspase-3 expression by Meto (P<001). PD98059 treatment had no significant effect on the increased p-Cx43 and cleaved caspase-3 expression induced by NE (P>005). CONCLUSION: The inhibitory effect of Meto on NE-induced cardiomyocyte apoptosis is related to the inhibition of Cx43 phosphorylation, which may be partly mediated via ERK1/2 pathway.  相似文献   

17.
AIM: To elucidate the effect of ginsenoside Rb1 (Gs-Rb1) on the glucose metabolism to improve the viability of the cardiomyocytes under hypoxia, and whether hypoxia-inducible factor 1α (HIF-1α) and/or AMPKα are involved in the process.METHODS: The neonatal rat cardiomyocytes were cultured, and randomly divided into control group, hypoxia (1% O2, 94% N2 and 5% CO2) group, Gs-Rb1 (200 μmol/L) group, Ara-A (500 μmol/L) group, Gs-Rb1+Ara-A group, YC-1 (5 μmol/L) group, Gs-Rb1+YC-1 group, Ara-A+YC-1 group and Gs-Rb1+YC-1+Ara-A group. After the intervention for 8 h, the cell viability was analyzed by MTT assay. The protein levels of AMPK, HIF-1α and glucose transporter-4 (GLUT-4) were determined by Western blot. The activities of heterophosphatase (HK), phosphofructokinase (PFK) and lactic dehydrogenase (LDH) were measured by ELISA.RESULTS: Gs-Rb1 significantly improved the viability of hypoxic cardiomyocytes, which was significantly inhibited by YC-1 and Ara-A. In addition, YC-1 and Ara-A had a synergistic effect. Gs-Rb1 increased the protein levels of AMPK and HIF-1α in the hypoxic cardiomyocytes, which was significantly inhibited by Ara-A and YC-1. Gs-Rb1 significantly increased the expression of GLUT-4 on the cytomembrane of hypoxic cardiomyocytes, which was significantly inhibited by YC-1 or Ara-A, especially Ara-A+YC-1. Gs-Rb1 significantly increased the activities of HK, PFK and LDH, all those were significantly inhibited by YC-1 or Ara-A. Besides, YC-1 and Ara-A had a synergistic effect.CONCLUSION: Gs-Rb1 improves the viability of hypoxic cardiomyocytes, which may be related to the regulation of glucose uptake and enhancement of glycolysis by synergy of both HIF-1α and AMPK.  相似文献   

18.
AIM: To explore the role of ubiquitin E3 ligase tripartite motif 10 (TRIM10) in the development of cardiomyocyte hypertrophy. METHODS: Primary cultured neonatal rat cardiomyocytes (NRCMs) were infected with siRNA-TRIM10, siRNA-control, Ad-TRIM10 or Ad-GFP for 24 h respectively, and then stimulated with phenylephrine (PE) for additional 24 h. The protein levels of TRIM10, AKT and ERK1/2 were determined by Western blot. The size of the NRCMs was measured by immunofluorescence staining. The mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was detected by RT-qPCR. RESULTS: Compared with the control, PE treatment significantly increased the protein expression of TRIM10. Moreover, transfection of NRCMs with siRNA-TRIM10 markedly inhibited cardiomyocyte size, the mRNA expression of ANP and BNP, and the phosphorylation levels of AKT and ERK as compared with siRNA-control after PE treatment. In contrast, overexpression of TRIM10 significantly enhanced PE-induced hypertrophic effect on NRCMs above. CONCLUSION: TRIM10 regulates cardiomyocyte hypertrophy partially through AKT and ERK signaling pathways.  相似文献   

19.
AIM: To study the role of prostaglandin F2α (PGF2α) in cardiac hypertrophy and its relation with calcineurin (CaN) signal transduction pathway in vitro. METHODS: The cultured neonatal rat cardiomyocyte was used to observe the hypertrophic effect of PGF2α, and the hypertrophic response was assayed by measuring the cell diameter, protein content and atrial natriuretic factor (ANF) mRNA expression. For mechanism studies, the intracellular free calcium concentration (［Ca2+］i) in cultured cardiomyocytes was measured by using Fura-2/AM as a fluorescent indicator. ANF and CaN mRNA expressions, and the expressions of CaN and its downstream effectors, NFAT3 and GATA4 proteins were assayed by RT-PCR and Western blotting, respectively.RESULTS: In cultured cardiomyocytes, PGF2α induced profound hypertrophic morphology change, the significant increase in cell diameter and protein content in a concentration-dependent manner compared with those in vehicle control (P<0.01). The same result was found in measuring the ［Ca2+］i in cardiomyocytes (P<0.01). PGF2α at concentration of 10-7 mol/L significantly promoted ANF and CaN mRNA expressions and the protein expressions of CaN/NFAT3/GATA4 compared with those in the vehicle control (P<0.05). Cyclosporin A, a CaN inhibitor, markedly inhibited the myocyte hypertrophy (P<0.01), reduced the increased ［Ca2+］i(P<0.01) and decreased the expressions of CaN mRNA and CaN/NFAT3/GATA4 proteins (P<0.05) compared with those of only PGF2α　10-7 mol/L treatment. CONCLUSION: Cardiomyocyte hypertrophy induced by PGF2α may be, at least in part, mediated by CaN signal transduction pathway activated by increasing ［Ca2+］i.  相似文献   

20.
AIM: To investigate the role of G-protein-coupled bile acid receptor 1(GPBR1; also known as TGR5) activation in high glucose-induced cardiomyocyte hypertrophy and calcineurin (CaN)/nuclear factor of activated T-cells 3 (NFAT3) signaling.METHODS: Primarily cultured mouse cardiomyocytes were used in the study. The cell surface areas of the cardiomyocytes were measured by an image analysis system. The cell protein content was detected by BCA method. The expression of TGR5, CaN and NFAT3 at mRNA and protein levels was determined by RT-PCR and Western blot.RESULTS: The mouse cardiomyocytes were successfully cultured. High glucose significantly induced the increases in the cell surface area, the cell protein content and the expression of CaN and NFAT3 (P<0.05) in the cardiomyocytes. TGR5 activation or a CaN antagonist cyclosporin A inhibited high glucose-induced cardiomyocyte hypertrophy and the expression of CaN and NFAT3 (P<0.05). These effects of TGR5 activation were abolished by TGR5 gene interference (P<0.05).CONCLUSION: TGR5 activation reduces high glucose-induced cardiomyocyte hypertrophy by inhibiting CaN/NFAT3 signaling.  相似文献   

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