Imbalance between CaM kinase II and calcineurin activities impairs caffeine-induced calcium release in hypertrophic cardiomyocytes

Lu, Ying; Shioda, Norifumi; Han, Feng; Moriguchi, Shigeki; Kasahara, Jiro; Shirasaki, Yasufumi; Qin, Zheng; Fukunaga, Kohji

doi:10.1016/j.bcp.2007.08.022

Cited by 23 publications

(35 citation statements)

References 64 publications

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“…31 The marked breakdown of dystrophin suggests involvement of calpain in OVX-PO-induced cardiac injury. We also found significant decrease in calpastatin levels after OVX-PO.…”

Section: Discussionmentioning

confidence: 99%

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

et al. 2009

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Abstract-We here investigated the effect of bis(1-oxy-2-pyridinethiolato) oxovanadium (IV), [VO(OPT)], against myocardial hypertrophy and cardiac functional recovery in pressure overload-induced hypertrophy in ovariectomized female rats and defined mechanisms underlying its cardioprotective action. Wistar rats subjected to bilateral ovariectomy were further treated with abdominal aortic stenosis. VO(OPT) (containing 1.25 and 2.50 mg of vanadium per kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. Treatment with VO(OPT) significantly inhibited pressure overload-induced increase both in the heart weight:body weight ratio and the lung weight:body weight ratio. VO(OPT) also attenuated hypertrophy-induced impaired left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contractility (Ϯdp/dt max ). VO(OPT) treatment significantly restored pressure overload-induced impaired endothelial NO synthase activity with concomitant increased phosphorylation of endothelial NO synthase (Ser1179). Moreover, VO(OPT) treatment significantly restored pressure overload-induced reduced Akt activity, as indicated by increased phosphorylation at Ser473 and at Thr308. Treatment with VO(OPT) also secondarily inhibited calpastatin and dystrophin breakdown and decreased myosin light chain phosphorylation. Finally, VO(OPT) treatment significantly attenuated mortality after repeated isoproterenol administration in pressure overloaded-ovariectomized rats. Taken together, VO(OPT) attenuates cardiac myocytes hypertrophy in vivo in pressure overload-induced hypertrophy in ovariectomized rats and prevents the process from hypertrophy to heart failure. These effects are mediated by inhibition of calpastatin and dystrophin breakdown in addition to increased Akt and endothelial NO synthase activities. Key Words: myocardial hypertrophy Ⅲ protein kinase B (Akt) Ⅲ endothelial nitric oxide synthase (eNOS) Ⅲ ovariectomy Ⅲ dystrophin L eft ventricular (LV) hypertrophy is an independent risk factor for the development of heart failure. 1 Although LV hypertrophy is an adaptive response to pressure and volume overload, this process becomes maladaptive without drug therapy. The pathological cardiac hypertrophy, in turn, triggers the development of heart failure. 2 The search for novel drug treatment has directed attention to cardiac hypertrophy as cardioprotection. 2 Signaling through the phosphatidylinositol 3-kinase/Akt pathway is important for the physiological growth and inhibition of pathological hypertrophy. 3-5 Moreover, physiological hypertrophy induced by exercise training also requires the activation of myocardial Akt. By contrast, pathological hypertrophies induced by pressure overload cause an inactivation of the Akt signal pathway. 6 We have also reported that pressure overload (PO)-induced hypertrophy in ovariectomized (OVX) female rats markedly reduces both endothelial NO synthase (eNOS) protein expression and its activity with concomitantly marked reduced Ak...

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“…31 The marked breakdown of dystrophin suggests involvement of calpain in OVX-PO-induced cardiac injury. We also found significant decrease in calpastatin levels after OVX-PO.…”

Section: Discussionmentioning

confidence: 99%

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

et al. 2009

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“…3). We previously documented that stimulation with angiotensin II, endothelin-1, and phenylephrine markedly increase calcineurin expression following hypertrophy in cultured rat cardiomyocytes (33). The transcriptional upregulation of calcineurin Aβ by endothelin-1 is partially mediated by activation of myocyte enhancer factor-2 (MEF2) by Ca 2+ /calmodulin-dependent protein kinase IIδ in rat cardiomyocytes (34).…”

Section: Possible Mechanism Of Ssri-mediated Cardioprotectionmentioning

confidence: 99%

Crucial Interactions Between Selective Serotonin Uptake Inhibitors and Sigma-1 Receptor in Heart Failure

2013

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Abstract. Depression is associated with a substantial increase in the risk of developing heart failure and is independently associated with increased cardiovascular morbidity and mortality. Inversely, cardiovascular disease can lead to severe depression. Thus, therapy with selective serotonin reuptake inhibitors (SSRIs) is strongly recommended to reduce cardiovascular diseaseinduced morbidity and mortality. However, molecular mechanisms to support evidence-based SSRI treatment of cardiovascular disease have not been elucidated. We recently found very high expression of the sigma-1 receptor, an orphan receptor, in rat heart tissue and defined the cardiac sigma-1 receptor as a direct SSRI target in eliciting cardioprotection in both pressure overload (PO)-induced and transverse aortic constriction (TAC)-induced myocardial hypertrophy models in rodents. Our findings suggest that SSRIs such as fluvoxamine protect against PO-and TACinduced cardiac dysfunction by upregulating sigma-1 receptor expression and stimulating sigma-1 receptor-mediated Akt-eNOS signaling. Here, we discuss the association of depression and cardiovascular diseases, the protective mechanism of SSRIs in heart failure patients, and the pathophysiological relevance of sigma-1 receptors to progression of heart failure. These findings should promote development of clinical therapeutics targeting the sigma-1 receptor in cardiovascular diseases.

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“…The cardiomyocyte cultures were isolated by enzy matic disassociation of 1 -3dayold neonatal rat hearts has been detailed previously (3). In brief, cardiomyocytes were cultured in 35mm dishes overnight in DMEM media supplemented with 10% fetal bovine serum, penicillin/streptomyocin (100 units/ml).…”

Section: Primary Cardiomyocytes Culture and Transfectionmentioning

confidence: 99%

“…The alternation in the intracellular Ca 2+ concentration is a primary stimulus for the cardiohypertrophic response (2,3). Calmodulin is a widespread transducer of intra cellular Ca 2+ signaling, which is considered to be influ enced by Ca 2+ ions.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of PEP-19 Suppresses Angiotensin II–Induced Cardiomyocyte Hypertrophy

et al. 2014

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Abstract. The precise molecular mechanisms leading to disturbance of Ca 2+ /calmodulin dependent intracellular signalling in cardiac hypertrophy remains unclear. As an endogenous calmodulin regulator protein, the pathophysiology role of PEP19 during cardiac hypertrophy was investigated in the present study. We here demonstrated that PEP19 protein levels are significantly elevated in the aortic banding model in vivo and angiotensin II-induced cardio myocyte hypertrophy in vitro. Consistent with inhibitory actions of PEP19 on cardiomyocyte hypertrophy, induction of CaMKII and calcineurin activation as well as hypertrophyrelated genes including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was significantly inhibited by PEP19 transfection. Moreover, PEP19 partially ameliorates angiotensin II-induced elevation of phosphophospholamban (Thr17) and sarcoplasmic reticulum Ca 2+ release in cardiomyocytes. Together, our results suggest that PEP19 attenuates angiotensin II-induced cardiomyocyte hypertrophy via suppressing the disturbance of CaMKII and calcineurin signaling.

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Imbalance between CaM kinase II and calcineurin activities impairs caffeine-induced calcium release in hypertrophic cardiomyocytes

Cited by 23 publications

References 64 publications

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

Crucial Interactions Between Selective Serotonin Uptake Inhibitors and Sigma-1 Receptor in Heart Failure

Overexpression of PEP-19 Suppresses Angiotensin II–Induced Cardiomyocyte Hypertrophy

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