Differential regulation of cardiac protein kinase C isozyme expression after aortic banding in rat

Braun, Martin; Rosée, Paul La; Schön, Steffen; Borst, Mathias M.; Strasser, Ruth H.

doi:10.1016/s0008-6363(02)00511-4

Cited by 47 publications

(30 citation statements)

References 54 publications

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“…Also, direct stimulation of PKC by phorbol esters mimicked the hypertrophic actions of NE (37). Aortic banding caused an upregulation of certain Ca 2+ -dependent and Ca 2+ -independent PKC isozymes in the LV and, after a delay, also in the RV (32). A similar delay of the RV response was observed in the present study with regard to the hypertrophic phenotype and also to the potentiation of the PDB-evoked PLD activation.…”

Section: +supporting

confidence: 86%

“…The RV hypertrophied much later, namely, >100 days after banding. A similar sequential LV and delayed RV hypertrophy following aortic banding had been described before (32). In the hypertrophic LV 30 -50 days after banding, the PLD activation caused by the α1-adrenoceptor agonist PE and by the phorbol ester PDB were markedly potentiated, whereas the basal PLD activity was only slightly increased.…”

Section: Discussionsupporting

confidence: 75%

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Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

Peivandi¹,

Huhn²,

Lehr³

et al. 2005

J Pharmacol Sci

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Abstract. Evidence for a role of phospholipase D (PLD) in cellular proliferation and differentiation is accumulating. We studied PLD activity and expression in normal and hypertrophic rat and human hearts. In rat heart, abdominal aortic banding (constriction to 50% of original lumen) caused hypertrophy in the left ventricle (as shown by weight index and ANP expression) by about 15% after 30 days without histological evidence of fibrosis or signs of decompensation and in the right ventricle after 100 days. The hypertrophy was accompanied by small increases of basal PLD activity and strong potentiation of stimulated PLD activity caused by 4β-phorbol-12β,13α-dibutyrate (PDB) and by phenylephrine. The mRNA expressions of both PLD1 and PLD2 determined by semiquantitative competitive RT-PCR were markedly enhanced after aortic banding. In the caveolar fraction of the rat heart, PLD2 protein determined by Western blot analysis was upregulated in parallel with the expression of caveolin-3. A similar induction of PLD mRNA and protein expression was observed in hypertrophied human hearts of individuals (39 -45-year-old) who had died from non-cardiac causes. In conclusion, PLD1 and PLD2 expressions were strongly enhanced both in rat and human heart hypertrophy, which may be responsible for the coincident potentiation of the PLD activation by α-adrenoceptor and protein kinase C stimulation. These results are compatible with a significant role of PLD activation in cell signaling of ventricular pressure-overload hypertrophy.

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Section: +supporting

confidence: 86%

Section: Discussionsupporting

confidence: 75%

Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

Peivandi¹,

Huhn²,

Lehr³

et al. 2005

J Pharmacol Sci

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“…2 However, previous studies have found increased or unaltered activation and expression of PKC-␣ in experimental models of LVH and CHF. 18,27,28 These divergent findings may relate to the duration (acute/compensated versus chronic/ end-stage) and/or etiology (myocardial infarction, pressure overload, volume overload, genetic hypertension) of heart disease. For these reasons, we examined PKC-␣ expression and activation in left ventricles obtained from rats in early HF and end-stage CHF.…”

Section: Pkc-␣ Expression and Activation In Experimental Chfmentioning

confidence: 99%

Augmented Protein Kinase C-α–Induced Myofilament Protein Phosphorylation Contributes to Myofilament Dysfunction in Experimental Congestive Heart Failure

Belin

Sumandea

Allen

et al. 2007

Circulation Research

139

150

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Abstract-It is becoming clear that upregulated protein kinase C (PKC) signaling plays a role in reduced ventricular myofilament contractility observed in congestive heart failure. However, data are scant regarding which PKC isozymes are involved. There is evidence that PKC-␣ may be of particular importance. Here, we examined PKC-␣ quantity, activity, and signaling to myofilaments in chronically remodeled myocytes obtained from rats in either early heart failure or end-stage congestive heart failure. Immunoblotting revealed that PKC-␣ expression and activation was unaltered in early heart failure but increased in end-stage congestive heart failure. Left ventricular myocytes were isolated by mechanical homogenization, Triton-skinned, and attached to micropipettes that projected from a force transducer and motor. Myofilament function was characterized by an active force- [Ca 2ϩ ] relation to obtain Ca 2ϩ -saturated maximal force (F max ) and myofilament Ca 2ϩ sensitivity (indexed by EC 50 ) before and after incubation with PKC-␣, protein phosphatase type 1 (PP1), or PP2a. PKC-␣ treatment induced a 30% decline in F max and 55% increase in the EC 50 in control cells but had no impact on myofilament function in failing cells. PP1-mediated dephosphorylation increased F max (15%) and decreased EC 50 (Ϸ20%) in failing myofilaments but had no effect in control cells. PP2a-dependent dephosphorylation had no effect on myofilament function in either group. Lastly, PP1 dephosphorylation restored myofilament function in control cells hyperphosphorylated with PKC-␣. Collectively, our results suggest that in end-stage congestive heart failure, the myofilament proteins exist in a hyperphosphorylated state attributable, in part, to increased activity and signaling of PKC-␣. Key Words: heart failure Ⅲ protein kinase C-␣ Ⅲ myofilament proteins Ⅲ protein phosphatase type 1 Ⅲ phosphorylation I t has been predicted that the global incidence and prevalence of the clinical syndrome of congestive heart failure (CHF) will continue to rise. 1 The "road" to CHF usually begins with some inciting event (eg, myocardial infarction), which imposes a heightened mechanical strain on the myocardium. Ventricular dysfunction ensues resulting in a decline in cardiac output. In turn, key regulatory neurohormonal signals are recruited, which, in the acute phase, maintain cardiac output and "mask" the underlying ventricular contractile deficit. However, prolonged exposure of the heart to these signals coupled with the prevailing mechanical overload proves deleterious resulting in contractile dysfunction, myocyte hypertrophy, and death, heralding a downward spiral wherein ventricular dysfunction becomes manifest and the clinical features of CHF overt. Not surprisingly, considerable attention is now being focused on unraveling the molecular and cellular complexities that conspire to promote contractile dysfunction of the failing cardiac myocyte, with the underlying aim being identification of novel molecules that may be potential foci for therapeutic inte...

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“…Previous studies have reported that the PKC␦ and -ε isoforms play an important role in cardiac hypertrophy (4,32). The PKCε activates ERK-AP-1 signaling pathway, leading to myocardial hypertrophy and increases in protein synthesis (28).…”

Section: Discussionmentioning

confidence: 99%

Diacylglycerol kinase-ε restores cardiac dysfunction under chronic pressure overload: a new specific regulator of Gα_qsignaling cascade

Niizeki¹,

Takeishi²,

Kitahara³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Galpha(q) protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in cardiac hypertrophy. DAG kinase (DGK) catalyzes DAG phosphorylation and controls cellular DAG levels, thus acting as a regulator of GPCR signaling. It has been reported that DGKepsilon acts specifically on DAG produced by inositol cycling. In this study, we examined whether DGKepsilon prevents cardiac hypertrophy and progression to heart failure under chronic pressure overload. We generated transgenic mice with cardiac-specific overexpression of DGKepsilon (DGKepsilon-TG) using an alpha-myosin heavy chain promoter. There were no differences in cardiac morphology and function between wild-type (WT) and DGKepsilon-TG mice at the basal condition. Either continuous phenylephrine infusion or thoracic transverse aortic constriction (TAC) was performed in WT and DGKepsilon-TG mice. Increases in heart weight after phenylephrine infusion and TAC were abolished in DGKepsilon-TG mice compared with WT mice. Cardiac dysfunction after TAC was prevented in DGKepsilon-TG mice, and the survival rate after TAC was higher in DGKepsilon-TG mice than in WT mice. Phenylephrine- and TAC-induced DAG accumulation, the translocation of PKC isoforms, and the induction of fetal genes were blocked in DGKepsilon-TG mouse hearts. The upregulation of transient receptor potential channel (TRPC)-6 expression after TAC was attenuated in DGKepsilon-TG mice. In conclusion, these results demonstrate the first evidence that DGKepsilon restores cardiac dysfunction and improves survival under chronic pressure overload by controlling cellular DAG levels and TRPC-6 expression. DGKepsilon may be a novel therapeutic target to prevent cardiac hypertrophy and progression to heart failure.

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Differential regulation of cardiac protein kinase C isozyme expression after aortic banding in rat

Abstract: This study characterizes in the right and left ventricle a differential regulation of the dominant PKC isozymes in pressure-overload cardiac hypertrophy both at the protein and the mRNA level.

Cited by 47 publications

References 54 publications

Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

Augmented Protein Kinase C-α–Induced Myofilament Protein Phosphorylation Contributes to Myofilament Dysfunction in Experimental Congestive Heart Failure

Diacylglycerol kinase-ε restores cardiac dysfunction under chronic pressure overload: a new specific regulator of Gα_qsignaling cascade

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Differential regulation of cardiac protein kinase C isozyme expression after aortic banding in rat

Abstract: This study characterizes in the right and left ventricle a differential regulation of the dominant PKC isozymes in pressure-overload cardiac hypertrophy both at the protein and the mRNA level.

Cited by 47 publications

References 54 publications

Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

Upregulation of Phospholipase D Expression and Activation in Ventricular Pressure-Overload Hypertrophy

Augmented Protein Kinase C-α–Induced Myofilament Protein Phosphorylation Contributes to Myofilament Dysfunction in Experimental Congestive Heart Failure

Diacylglycerol kinase-ε restores cardiac dysfunction under chronic pressure overload: a new specific regulator of Gαqsignaling cascade

Contact Info

Product

Resources

About

Diacylglycerol kinase-ε restores cardiac dysfunction under chronic pressure overload: a new specific regulator of Gα_qsignaling cascade