Protein kinase C-α-induced hypertrophy of neonatal rat ventricular myocytes

Vijayan, Kalpana; Szotek, Erika L.; Martin, J.L.; Samarel, Allen M.

doi:10.1152/ajpheart.00171.2004

Cited by 42 publications

(43 citation statements)

References 37 publications

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“…In addition, PKCα regulates the hypertrophic growth of cardiomyocytes through ERK1/2 [18]. Consistent with the results of previous studies [11,24], we also found that the overexpression of either myocardin or PKCα increased the cell surface area and induced cardiac hypertrophy. Furthermore, we examined the relationship between two transcription factors, myocardin and PKCα, in the regulation of cardiomyocyte hypertrophy.…”

Section: Discussionsupporting

confidence: 92%

Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Wang

et al. 2015

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Myocardin plays a key role in the development of cardiac hypertrophy. However, the upstream signals that control the stability and transactivity of myocardin remain to be fully understood. The expression of protein kinase Cα (PKCα) also induces cardiac hypertrophy. An essential downstream molecule of PKCα, extracellular signal-regulated kinase 1/2, was reported to negatively regulate the activities of myocardin. But, the effect of cooperation between PKCα and myocardin and the potential molecular mechanism by which PKCα regulates myocardin-mediated cardiac hypertrophy are unclear. In this study, a luciferase assay was performed using H9C2 cells transfected with expression plasmids for PKCα and myocardin. Surprisingly, the results showed that PKCα inhibited the transcriptional activity of myocardin. PKCα inhibited myocardin-induced cardiomyocyte hypertrophy, demonstrated by the decrease in cell surface area and fetal gene expression, in cardiomyocyte cells overexpressing PKCα and myocardin. The potential mechanism underlying the inhibition effect of PKCα on the function of myocardin is further explored. PKCα directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues. In myocardin-overexpressing cardiomyocyte cells, PKCα induced the excessive phosphorylation of myocardin, resulting in the degradation of myocardin and a transcriptional suppression of hypertrophic genes. These results demonstrated that PKCα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation.

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Section: Discussionsupporting

confidence: 92%

Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Wang

et al. 2015

ABBS

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“…PMA Induces GRK5 Protein Levels and Increases Binding Activity of NF-B to the GRK5 Promoter in Myocytes-PMA is a specific activator of PKC (23), which can activate NF-B through PKC as well as through the induced formation of reactive oxygen species (ROS) (24). PMA is a well established hypertrophic agent in myocytes and, accordingly, was tested to determine whether it could induce GRK5 expression in NRVMs.…”

Section: Nf-b Proteins P50 and P65 Interact With The Promotermentioning

confidence: 99%

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Islam

Koch²

2012

Journal of Biological Chemistry

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Background: GRK5 up-regulation and NF-B activation have been shown to be associated with heart disease. Results: NF-B activation in cardiomyocytes promotes stress-induced GRK5 up-regulation. Conclusion: NF-B activation by hypertrophic stimuli/ROS leads to increased binding of NF-B (p50/p65) to the GRK5 promoter, thereby enhancing myocardial GRK5 expression. Significance: NF-B regulation of GRK5 in myocytes may translate to the significant expression changes seen in heart disease.

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“…The conventional PKC isozymes, comprising, ␣, ␤I, ␤II, and ␥, are activated by Ca 2ϩ , phosphatidylserine, diacylglycerol, or phorbol esters; the novel PKC isozymes, consisting of PKC␦, -⑀, -, -, and -, are activated by phosphatidylserine, diacylglycerol, or phorbol esters, but insensitive to Ca 2ϩ ; and the atypical isoforms ( and /) are dependent on phosphatidylserine for activation, but not affected by Ca 2ϩ , diacylglycerol, or phorbol esters (1-3). Activated PKC translocates from cytosol to membranous organelles and/or to the nucleus (4,5). In addition, oxidative stress has been reported to induce prolonged activation of PKC within the cells (6 -9).…”

Section: Pkcmentioning

confidence: 99%

Phosphorylated Extracellular Signal-regulated Protein Kinases 1 and 2 Phosphorylate Sp1 on Serine 59 and Regulate Cellular Senescence via Transcription of p21Sdi1/Cip1/Waf1

Kim

Lim

2009

Journal of Biological Chemistry

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Expression of p21Sdi1 downstream of p53 is essential for induction of cellular senescence, although cancer cell senescence can also occur in the p53 null condition. We report herein that senescence-associated phosphorylated extracellular signal-regulated protein kinases 1 and 2 (SA-pErk1/2) enhanced p21 Sdi1 transcription by phosphorylating Sp1 on Ser 59 downstream of protein kinase C (PKC) ␣. Reactive oxygen species (ROS), which was increased in cellular senescence, significantly activated both PKC␣ and PKC␤I. However, PKC␣, but not PKC␤I, regulated ROS generation and cell proliferation in senescent cells along with activation of cdk2, proven by siRNAs. PKC␣-siRNA also reduced SA-pErk1/2 expression in old human diploid fibroblast cells, accompanied with changes of senescence phenotypes to young cell-like. Regulation of SA-pErk1/2 was also confirmed by using catalytically active PKC␣ and its DN-mutant construct. These findings strongly suggest a new pathway to regulate senescence phenotypes by ROS via Sp1 phosphorylation between PKC␣ and SA-pErk1/2: employing GST-Sp1 mutants and MEK inhibitor analyses, we found that SA-pErk1/2 regulated Sp1 phosphorylation on the Ser 59 residue in vivo, but not threonine, in cellular senescence, which regulated transcription of p21 Sdi1 expression. In summary, PKC␣, which was activated in senescent cells by ROS strongly activated Erk1/2, and the SA-pErk1/2 in turn phosphorylated Sp1 on Ser 59. Sp1-enhanced transcription of p21 Sdi1 resulted in regulation of cellular senescence in primary human diploid fibroblast cells. PKC3 comprises a family of serine/threonine kinase that modulates a variety of signal transduction pathways, leading to gene expression, cell proliferation, and differentiation. PKC isoforms are classified into three subgroups. The conventional PKC isozymes, comprising, ␣, ␤I, ␤II, and ␥, are activated by Ca 2ϩ , phosphatidylserine, diacylglycerol, or phorbol esters; the novel PKC isozymes, consisting of PKC␦, -⑀, -, -, and -, are activated by phosphatidylserine, diacylglycerol, or phorbol esters, but insensitive to Ca 2ϩ ; and the atypical isoforms ( and /) are dependent on phosphatidylserine for activation, but not affected by Ca 2ϩ , diacylglycerol, or phorbol esters (1-3). Activated PKC translocates from cytosol to membranous organelles and/or to the nucleus (4, 5). In addition, oxidative stress has been reported to induce prolonged activation of PKC within the cells (6 -9). The growth regulatory consequences of PKC activation suggest a link between PKC signaling and control of the cell cycle machinery. Activation of PKC has been shown to result in alterations of cell cycle progression in either stimulatory or inhibitory directions in several systems (10 -15). Among the isoforms, PKC␣ has been implicated in the control of G 1 /S transition (14, 16 -18) and recently in the regulation of cancer cell senescence (19), whereas PKC␤II has been shown to play a role in progression from G 2 into M phase (15), and PKC␦ has been associated with the control of M phase (2...

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Protein kinase C-α-induced hypertrophy of neonatal rat ventricular myocytes

Abstract: . Protein kinase C-␣-induced hypertrophy of neonatal rat ventricular myocytes.

Cited by 42 publications

References 37 publications

Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Phosphorylated Extracellular Signal-regulated Protein Kinases 1 and 2 Phosphorylate Sp1 on Serine 59 and Regulate Cellular Senescence via Transcription of p21Sdi1/Cip1/Waf1

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Protein kinase C-α-induced hypertrophy of neonatal rat ventricular myocytes

Abstract: . Protein kinase C-␣-induced hypertrophy of neonatal rat ventricular myocytes.

Cited by 42 publications

References 37 publications

Protein kinase C&alpha; inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Protein kinase C&alpha; inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Involvement of Nuclear Factor κB (NF-κB) Signaling Pathway in Regulation of Cardiac G Protein-coupled Receptor Kinase 5 (GRK5) Expression

Phosphorylated Extracellular Signal-regulated Protein Kinases 1 and 2 Phosphorylate Sp1 on Serine 59 and Regulate Cellular Senescence via Transcription of p21Sdi1/Cip1/Waf1

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Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation

Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation