ag-490 and Cardiomegaly

ag-490 has been researched along with Cardiomegaly* in 4 studies

Other Studies

4 other study(ies) available for ag-490 and Cardiomegaly

ArticleYear
GJA1-20k attenuates Ang II-induced pathological cardiac hypertrophy by regulating gap junction formation and mitochondrial function.
    Acta pharmacologica Sinica, 2021, Volume: 42, Issue:4

    Cardiac hypertrophy (CH) is characterized by an increase in cardiomyocyte size, and is the most common cause of cardiac-related sudden death. A decrease in gap junction (GJ) coupling and mitochondrial dysfunction are important features of CH, but the mechanisms of decreased coupling and energy impairment are poorly understood. It has been reported that GJA1-20k has a strong tropism for mitochondria and is required for the trafficking of connexin 43 (Cx43) to cell-cell borders. In this study, we investigated the effects of GJA1-20k on Cx43 GJ coupling and mitochondrial function in the pathogenesis of CH. We performed hematoxylin-eosin (HE) and Masson staining, and observed significant CH in 18-week-old male spontaneously hypertensive rats (SHRs) compared to age-matched normotensive Wistar-Kyoto (WKY) rats. In cardiomyocytes from SHRs, the levels of Cx43 at the intercalated disc (ID) and the expression of GJA1-20k were significantly reduced, whereas JAK-STAT signaling was activated. Furthermore, the SHR rats displayed suppressed mitochondrial GJA1-20k and mitochondrial biogenesis. Administration of valsartan (10 mg· [Formula: see text] d

    Topics: Angiotensin II; Animals; Cardiomegaly; Connexin 43; Down-Regulation; Gap Junctions; Janus Kinase 2; Male; Membrane Potential, Mitochondrial; Mitochondria; Myocardium; Organelle Biogenesis; Rats, Inbred WKY; Reactive Oxygen Species; Signal Transduction; Tyrphostins; Valsartan

2021
Pressure overload-induced cardiac hypertrophy response requires janus kinase 2-histone deacetylase 2 signaling.
    International journal of molecular sciences, 2014, Nov-05, Volume: 15, Issue:11

    Pressure overload induces cardiac hypertrophy through activation of Janus kinase 2 (Jak2), however, the underlying mechanisms remain largely unknown. In the current study, we tested whether histone deacetylase 2 (HDAC2) was involved in the process. We found that angiotensin II (Ang-II)-induced re-expression of fetal genes (Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) in cultured cardiomyocytes was prevented by the Jak2 inhibitor AG-490 and HDAC2 inhibitor Trichostatin-A (TSA), or by Jak2/HDAC2 siRNA knockdown. On the other hand, myocardial cells with Jak2 or HDAC2 over-expression were hyper-sensitive to Ang-II. In vivo, pressure overload by transverse aorta binding (AB) induced a significant cardiac hypertrophic response as well as re-expression of ANP and BNP in mice heart, which were markedly reduced by AG-490 and TSA. Significantly, AG-490, the Jak2 inhibitor, largely suppressed pressure overload-/Ang-II-induced HDAC2 nuclear exportation in vivo and in vitro. Meanwhile, TSA or HDAC2 siRNA knockdown reduced Ang-II-induced ANP/BNP expression in Jak2 over-expressed H9c2 cardiomyocytes. Together, these results suggest that HDAC2 might be a downstream effector of Jak2 to mediate cardiac hypertrophic response by pressure overload or Ang-II.

    Topics: Active Transport, Cell Nucleus; Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiomegaly; Cell Nucleus; Cells, Cultured; Histone Deacetylase 2; Hydroxamic Acids; Janus Kinase 2; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peptide Fragments; Pressure; Rats; Signal Transduction; Tyrphostins

2014
Inhibition of Jak2 phosphorylation attenuates pressure overload cardiac hypertrophy.
    Vascular pharmacology, 2006, Volume: 45, Issue:6

    We examined the role of Jak2 kinase phosphorylation in the development of pressure overload hypertrophy in mice subjected to transverse aortic constriction (TAC) and treated with tyrphostin AG490, a pharmacological inhibitor of Jak2.. Control mice (sham), subjected to TAC for 15 days (TAC) or to TAC and treated with 48 microg/kg/day i.p. of tyrphostin AG490 (TAC+AG490) were evaluated for morphological, physiological, and molecular changes associated with pressure overload hypertrophy.. Mice subjected to TAC alone developed concentric hypertrophy that accompanied activation of the components of the Jak/STAT signaling pathway manifested by an increase in phosphorylation of Jak2 and STAT3. We also observed increased phosphorylation of MAPK p44/p42, p38 MAPK and JNK in the TAC group, as well as, an increase in expression of MKP-1 phosphatase which negatively regulates MAPK kinases. Treatment of aortic constricted mice with tyrphostin AG490 failed to develop hypertrophy and showed a marked reduction in phosphorylation of Jak2 and STAT3. There was, however, in TAC and AG490 treated mice, a notable increase in the phosphorylation state of the MAPK p44/42, whereas MKP-1 phosphatase was downregulated.. These findings suggest that Jak2 kinase plays an important role in left ventricular remodeling during pressure overload hypertrophy. Pharmacological inhibition of Jak2 kinase during pressure overload blocks the development of concentric hypertrophy.

    Topics: Actins; Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Blood Pressure; Cardiomegaly; Disease Models, Animal; Echocardiography; Heart Ventricles; Janus Kinase 2; Ligation; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Phosphorylation; Protein Kinase Inhibitors; RNA, Messenger; STAT3 Transcription Factor; Tyrphostins; Ventricular Function, Left; Ventricular Myosins; Ventricular Remodeling

2006
Significance of ERK cascade compared with JAK/STAT and PI3-K pathway in gp130-mediated cardiac hypertrophy.
    American journal of physiology. Heart and circulatory physiology, 2000, Volume: 279, Issue:4

    We compared the role of the Raf-1/mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated protein kinase (ERK)/p90(RSK) cascade in gp130-mediated cardiac hypertrophy with the contribution of the Janus kinase (JAK)/signal transduction and activation of transcription (STAT) and phosphatidylinositide 3-kinase (PI3-K) pathways. Primary cultured neonatal rat cardiomyocytes were stimulated with leukemia inhibitory factor (LIF). LIF sequentially activated Raf-1, MEK1/2, ERK1/2, and p90(RSK). We used PD-98059 (a specific MEK inhibitor), AG-490 (a JAK2 inhibitor), and wortmannin (a PI3-K inhibitor) to confirm that this cascade was independent of the JAK/STAT and PI3-K/p70 S6 kinase (S6K) pathways. PD-98059, AG-490, and wortmannin suppressed the LIF-induced increase in [(3)H]phenylalanine uptake by 54.7, 21.5, and 25.6%, respectively, and inhibited the increase in cell area by 61.2, 42.8, and 39.2%, respectively. Reorganization of myofilaments was predominantly suppressed by AG-490. LIF-induced expression of c-fos, brain natriuretic peptide, and skeletal alpha-actin mRNA was markedly suppressed by PD-98059 and moderately suppressed by wortmannin and AG-490. Atrial natriuretic peptide was significantly suppressed by AG-490. These findings indicate that this pathway is critically involved in protein synthesis, induction of c-fos, brain natriuretic peptide, and skeletal alpha-actin expression and is partially involved in myofilament reorganization and atrial natriuretic peptide induction in gp130-mediated cardiac hypertrophy.

    Topics: Androstadienes; Animals; Antigens, CD; Cardiomegaly; Cell Size; Cells, Cultured; Cytokine Receptor gp130; Flavonoids; Genetic Markers; Growth Inhibitors; Interleukin-6; Leukemia Inhibitory Factor; Lymphokines; Membrane Glycoproteins; Mitogen-Activated Protein Kinases; Myocardium; Phenylalanine; Phosphatidylinositol 3-Kinases; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-raf; Rats; Rats, Wistar; Ribosomal Protein S6 Kinases; Signal Transduction; Trans-Activators; Tyrphostins; Wortmannin

2000
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