Modulation of the caveolin-3 localization to caveolae and STAT3 to mitochondria by catecholamine-induced cardiac hypertrophy in H9c2 cardiomyoblasts

Jeong, Kyuho; Kwon, Hayeong; Min, Chanhee; Pak, Yunbae

doi:10.3858/emm.2009.41.4.025

Cited by 39 publications

(41 citation statements)

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“…Unlike these receptors, β 2 ARs can be confined into the caveolae, where they are coupled with G i protein, thus impairing cAMP production and activating a pro-survival pathway 33,[35][36][37] . Chronic βAR over-stimulation also induces the downregulation of caveolin-3 38 , the structural component of caveolae, allowing β 2 AR to move out of caveolae where they mediate the same effects of β 1 AR 33,35,39 .…”

Section: Discussionmentioning

confidence: 97%

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Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

et al. 2015

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We investigated the effect of α-linolenic acid (ALA) in protecting the heart from injury caused by β-adrenergic overstimulation. ALA's role either in isoproterenol (ISO)-treated isolated rat cardiomyocytes (H9c2 cells) or in in vivo rat hearts was studied. In isolated cardiomyocytes in vitro, the involvement of kinases (Src and PI3K) in protection was tested using the specific inhibitors (PP2 or LY294002 respectively), while the role of caveolae was assessed by their disruption with methyl-β-cyclodextrin. The rats underwent either a normal chow diet or, alternatively, an ALA-enriched diet before, during and throughout the 60 days after 5 days of isoproterenol administration. Before sacrifice, the hemodynamic changes were measured using echocardiography. In the explanted hearts, histological changes together with molecular markers of cardiac fibrosis and hypertrophy were evaluated. In H9c2 cells, ALA abolished the ISO-induced reduction of viability. This effect was suppressed by both the inhibitor PP2 or LY294002 and the caveolae disrupter methyl-β-cyclodextrin. In the rats, ALA prevented ISO-induced myocardial fibrosis and hypertrophy and kept the cardiac mechanical function as in the control. It also counteracted the increased expressions of transforming growth factor-β (TGF-β) and β-myosin (β-MHC), the decreased expression of tissue inhibitor metalloproteinase-1 (TIMP-1) and the enhanced activity of matrix metalloproteinase-2 (MMP-2). In conclusion, ALA-induced protection requires the integrity of caveolae where β2-adrenergic receptors (β2ARs) are restricted and mediate the activation of the Src-PI3K protective pathway. By preserving this β2AR pro-survival pathway, an ALA-enriched diet protects the heart against ISO-induced fibrosis and hypertrophy.

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Section: Discussionmentioning

confidence: 97%

“…ISO administration was reported to reduce caveolin-3 expression and caveolae density 33,38,[41][42][43] .…”

Section: Discussionmentioning

confidence: 98%

Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

et al. 2015

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“…For instance, STAT3 has been found to interact with GRIM-19, a known component of mitochondrial complex I (17,18) and to regulate mitochondrial complex function of the respiratory chain in primary pro-B lymphocytes and the heart (19,20). More recently, Jeong et al (21) reported that catecholamine-induced hypertrophy modulates the expression and activation of STAT3 in mitochondria of cardiomyocytes. In light of these and related observations, an understanding of the role for SIRT1-STAT3 connection in mitochondria respiration is important.…”

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confidence: 98%

Negative Regulation of STAT3 Protein-mediated Cellular Respiration by SIRT1 Protein

Bernier¹,

Paul²,

Martín-Montalvo³

et al. 2011

Journal of Biological Chemistry

119

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In mammals, the transcriptional activity of signal transducer and activator of transcription 3 (STAT3) is regulated by the deacetylase SIRT1. However, whether the newly described nongenomic actions of STAT3 toward mitochondrial oxidative phosphorylation are dependent on SIRT1 is unclear. In this study, Sirt1 gene knock-out murine embryonic fibroblast (MEF) cells were used to delineate the role of SIRT1 in the regulation of STAT3 mitochondrial function. Here, we show that STAT3 mRNA and protein levels and the accumulation of serine-phosphorylated STAT3 in mitochondria were increased significantly in Sirt1-KO cells as compared with wild-type MEFs. Various mitochondrial bioenergetic parameters, such as the oxygen consumption rate in cell cultures, enzyme activities of the electron transport chain complexes in isolated mitochondria, and production of ATP and lactate, indicated that Sirt1-KO cells exhibited higher mitochondrial respiration as compared with wildtype MEFs. Two independent approaches, including ectopic expression of SIRT1 and siRNA-mediated knockdown of STAT3, led to reduction in intracellular ATP levels and increased lactate production in Sirt1-KO cells that were approaching those of wild-type controls. Comparison of profiles of phospho-antibody array data indicated that the deletion of SirT1 was accompanied by constitutive activation of the proinflammatory NF-B pathway, which is key for STAT3 induction and increased cellular respiration in Sirt1-KO cells. Thus, SIRT1 appears to be a functional regulator of NF-B-dependent STAT3 expression that induces mitochondrial biogenesis. These results have implications for understanding the interplay between STAT3 and SIRT1 in pro-inflammatory conditions.Sirtuins, or silent information regulator proteins, are a conserved family of seven proteins that regulate distinct biological pathways in mammals (1). The sirtuin, SIRT1, a NAD-dependent deacetylase, is located in the nucleus and plays crucial roles in genome organization and stability, stress response, glucose homeostasis, cell differentiation, DNA repair, and cell cycle control (2, 3). It also regulates processes such as cell survival, inflammation, mitochondrial biogenesis, and oxidative damage (4). Although the promotion of mitochondrial biogenesis by SIRT1 has been ascribed to deacetylation of the master regulator PGC-1␣ and FOXO1 (5, 6), little is known about how SIRT1 controls the energy production of the cell. Proper mitochondrial function is crucial for maintenance of metabolic homeostasis and activation of appropriate stress responses that have been implicated in life span extension and aging (7). The process of oxidative phosphorylation to generate ATP represents one of the principal bioenergetic functions of mitochondria, and yet the molecular mechanisms by which deregulation of SIRT1 expression and/or activity alters the capacity of mitochondria to meet energy demands have only begun to be elucidated.The signal transducer and activator of transcription 3 (STAT3) transcription factor is a key antiapo...

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“…The features of cardiac hypertrophy include enlarged cardiomyocyte size, increased protein synthesis, elevated fetal gene atrial natriuretic peptide, brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) expression, and abnormal sarcomeric organization, as well as heightened expression of fibronectin. There are numerous cell signaling pathways associated with cardiac hypertrophy and cardiac failure, including signal transducer and activator of transcription 3, Akt, extracellular signal-regulated kinase (ERK)1/2 and liver kinase B1/5' AMP-activated protein kinase (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…When the cells reached 70-80% confluence, they were passaged according to a 1:2 proportion and the medium was changed every 2 days. Cells were seeded into a 35-mm dish at a density of 1x10 5 . Cells were cultured in serum-free medium (GE Healthcare Life Sciences, Logan, UT, USA) at 37˚C overnight and pretreated with 100 nM apelin for 2 h, followed by treatment with 50 ng/ml resistin for 1 or 48 h.…”

Section: Introductionmentioning

confidence: 99%

Resistin-induced cardiomyocyte hypertrophy is inhibited by apelin through the inactivation of extracellular signal-regulated kinase signaling pathway in H9c2 embryonic rat cardiomyocytes

et al. 2016

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Abstract. It has been reported that resistin induces, whereas apelin inhibits cardiac hypertrophy. However, the underlying molecular mechanisms of apelin inhibiting resistin-induced cardiac hypertrophy remain unclear. The aim of the current study is to investigate the effects of apelin on resistin-induced cardiomyocyte hypertrophy and elucidate the underlying molecular mechanism. H9c2 cells were used in the present study, and cell surface area and protein synthesis were evaluated. Reverse transcription-quantitative polymerase chain reaction was performed to analyze the expression levels of hypertrophic markers, brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC). In addition, western blotting was conducted to examine phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Following treatment of H9c2 cells with resistin, cell surface area, protein synthesis, and BNP and β-MHC mRNA expression levels were increased. Subsequent to co-treatment of H9c2 cells with apelin and resistin, lead to the inhibition of resistin-induced hypertrophic effects by apelin. In addition, treatment with resistin increased phosphorylation of ERK1/2, whereas pretreatment with apelin decreased phosphorylation of ERK1/2, which was increased by resistin. These results indicate that resistin-induced cardiac hypertrophy is inhibited by apelin via inactivation of ERK1/2 cell signaling.

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Modulation of the caveolin-3 localization to caveolae and STAT3 to mitochondria by catecholamine-induced cardiac hypertrophy in H9c2 cardiomyoblasts

Cited by 39 publications

References 39 publications

Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation

Negative Regulation of STAT3 Protein-mediated Cellular Respiration by SIRT1 Protein

Resistin-induced cardiomyocyte hypertrophy is inhibited by apelin through the inactivation of extracellular signal-regulated kinase signaling pathway in H9c2 embryonic rat cardiomyocytes

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