Peptide growth factors signal differentially through protein kinase C to extracellular signal-regulated kinases in neonatal cardiomyocytes

Clerk, Angela; Aggeli, Ioanna-Katerina; Σταθοπούλου, Κωνσταντίνα; Sugden, Peter H.

doi:10.1016/j.cellsig.2005.04.005

Cited by 69 publications

(73 citation statements)

References 31 publications

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“…Furthermore, decreased levels of Mfn2 in MEFs increased the phosphorylation of ERK1/2 (de Brito and Scorrano, 2009), and activation of ERK1/2 is known to be sufficient to promote a hypertrophic growth in cardiomyocytes (Ramirez et al, 1997;Bueno et al, 2000;Clerk et al, 2006). Mfn2 also participates in the interaction between mitochondria and ER, which is essential for maintaining proper mitochondrial Ca 2+ uptake and the subsequent stimulation of mitochondrial metabolism (de Brito and Scorrano, 2009;Cárdenas et al, 2010;Bravo et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Pennanen

Parra

López-Crisosto

et al. 2014

Journal of Cell Science

136

152

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Cardiomyocyte hypertrophy has been associated with diminished mitochondrial metabolism. Mitochondria are crucial organelles for the production of ATP, and their morphology and function are regulated by the dynamic processes of fusion and fission. The relationship between mitochondrial dynamics and cardiomyocyte hypertrophy is still poorly understood. Here, we show that treatment of cultured neonatal rat cardiomyocytes with the hypertrophic agonist norepinephrine promotes mitochondrial fission (characterized by a decrease in mitochondrial mean volume and an increase in the relative number of mitochondria per cell) and a decrease in mitochondrial function. We demonstrate that norepinephrine acts through a 1 -adrenergic receptors to increase cytoplasmic Ca 2+ , activating calcineurin and promoting migration of the fission protein Drp1 (encoded by Dnml1) to mitochondria. Dominant-negative Drp1 (K38A) not only prevented mitochondrial fission, it also blocked hypertrophic growth of cardiomyocytes in response to norepinephrine. Remarkably, an antisense adenovirus against the fusion protein Mfn2 (AsMfn2) was sufficient to increase mitochondrial fission and stimulate a hypertrophic response without agonist treatment. Collectively, these results demonstrate the importance of mitochondrial dynamics in the development of cardiomyocyte hypertrophy and metabolic remodeling.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Pennanen

Parra

López-Crisosto

et al. 2014

Journal of Cell Science

136

152

View full text Add to dashboard Cite

show abstract

“…Mutated MEK1 was found in a few CFC patients with signs of HCM (13). Evidence from cultured cardiac myocytes exposed to a MEK1-specific inhibitor demonstrated the critical contribution of the ERK pathway to hypertrophy (62,63). In vivo, inhibition of MEK attenuated cardiac growth in both induced and genetic models of hypertrophy (48,59,64,65).…”

Section: Pathophysiological Signaling: Experimental Relevance Of the mentioning

confidence: 99%

Signaling to Cardiac Hypertrophy: Insights from Human and Mouse RASopathies

Sala

Gallo

Leo

et al. 2012

Mol Med

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“…Evidence from cultured cardiac myocytes using an MEK-1-specific inhibitor and comprehensive cDNA gene expression profiling demonstrated the critical contribution of the ERK pathway to hypertrophic gene expression induced by prohypertrophic agonists. 46,47 In addition to the canonical tyrosine kinase receptor-mediated activation by peptide growth factors, ERK pathway can be induced in heart muscle cells by prohypertrophic hormones such as ␣-adrenergic receptor agonists, through G␣q/protein kinase C pathways, 48,49 or by ␤-adrenergic agonists via direct interaction between ERK and ␤-arrestin. 50,51 Direct oxidative modification of thiol groups in Ras also is reported to be important in its activation by hypertrophic stimulation.…”

Section: Erk Pathway In Cardiac Hypertrophymentioning

confidence: 99%

Mitogen-Activated Protein Kinases in Heart Development and Diseases

2007

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Abstract-Mitogen-activated protein (MAP) kinases belong to a highly conserved family of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological functions. The 4 best-characterized MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, have been implicated in different aspects of cardiac regulation, from development to pathological remodeling. Recent advancements in the development of kinase-specific inhibitors and genetically engineered animal models have revealed significant new insights about MAP kinase pathways in the heart. However, this explosive body of new information also has yielded many controversies about the functional role of specific MAP kinases as either detrimental promoters or critical protectors of the heart during cardiac pathological processes. These uncertainties have raised questions on whether/how MAP kinases can be targeted to develop effective therapies against heart diseases. In this review, recent studies examining the role of MAP kinase subfamilies in cardiac development, hypertrophy, and survival are summarized.

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Peptide growth factors signal differentially through protein kinase C to extracellular signal-regulated kinases in neonatal cardiomyocytes

Cited by 69 publications

References 31 publications

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Mitochondrial fission is required for cardiomyocyte hypertrophy via a Ca2+-calcineurin signalling pathway

Signaling to Cardiac Hypertrophy: Insights from Human and Mouse RASopathies

Mitogen-Activated Protein Kinases in Heart Development and Diseases

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