Sarcoplasmic reticulum Ca 2+ load in human heart failure

Pieske, Burkert; Maier, Lars S.; Schmidt‐Schweda, Stephan

doi:10.1007/s003950200032

Cited by 37 publications

(37 citation statements)

References 20 publications

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“…However, within the same Western blots or immunoprecipitates, other tissues (e.g., human pulmonary artery and porcine ASM) displayed significant PLB levels. Specificity of the PLB antibody for human PLB has been previously demonstrated by other groups (21,24) and also confirmed by using positive controls from both human and other species in the present study. Accordingly, it is likely that although PLB mRNA is present in human ASM, the mRNA is not being translated, or if it is, the extent of translation or the level of stable protein is minimal (as suggested by the miniscule amount noted with immunoprecipitation of large amounts of ASM protein).…”

Section: Discussionsupporting

confidence: 89%

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca²⁺reuptake in human airway smooth muscle

Sathish¹,

Thompson²,

Bailey³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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([Ca 2ϩ ] i ) is key to contractility of airway smooth muscle (ASM). Studies from our own laboratory and by others showed that proinflammatory cytokines such as TNF␣ and IL-13 increase agonist-induced [Ca 2ϩ ] i response in ASM (8,31,35,38). The sarcoplasmic reticulum (SR) is a specialized intracellular membrane system in smooth and striated muscle that is involved in the uptake, storage, and release of Ca . In smooth muscle (as in other muscles), the SR Ca 2ϩ ATPase (SERCA) is the sole mechanism for replenishing SR Ca 2ϩ stores, with two Ca 2ϩ ions pumped into the SR for every ATP consumed against a Ca 2ϩ gradient of ϳ1 M in the cytosol vs. 1 mM in the SR lumen (16,22). Thus, inflammation-induced increase in [Ca 2ϩ ] i may be mediated by interference with SERCA expression and function such that SR Ca 2ϩ reuptake is impaired. There is currently very limited data on the regulation of SERCA in ASM (7,17,30). In cardiac muscle, SERCA is normally modulated in an inhibitory fashion by the protein phospholamban (PLB) (33). Previous studies in bovine pulmonary artery (26) and murine gastrointestinal smooth muscle (14) have shown that, as in cardiac muscle, cyclic nucleotides, Ca 2ϩ /CaM-dependent protein kinase (CaMKII), and/or protein kinase C phosphorylate PLB, resulted in disinhibition of SERCA and accelerated SR Ca 2ϩ reuptake. However, in porcine coronary artery smooth muscle, while there is evidence of CaMKII phosphorylation of SERCA with accompanying increase in SERCA activity, PLB has not been detected in that tissue (12). In this regard, whether PLB itself regulates SERCA in ASM (as in cardiac or other smooth muscles) is not at all clear. We recently reported that porcine ASM does express PLB, that PLB regulation by CaMKII occurs, and decreased PLB expression (using small interference RNA; siRNA) increases SR Ca 2ϩ refilling following agonist exposure (30). However, in that study, we found that even with PLB suppression by siRNA, additional modulation of Ca 2ϩ reuptake can occur via CaMKII. Accordingly, the expression and contribution of PLB to SR Ca 2ϩ refilling may be tissue-and speciesspecific. In this regard, there is currently no information on SERCA regulation by PLB in human ASM. Furthermore, there is no information on alterations in SERCA with airway inflammation that could contribute to increased [Ca 2ϩ ] i and thus increased bronchoconstriction.In the present study, we hypothesized that inflammation leads to increased PLB expression and inhibition of SERCA in human ASM, thus decreasing SR Ca 2ϩ reuptake and contributing to inflammation-induced increase in [Ca 2ϩ

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Section: Discussionsupporting

confidence: 89%

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca²⁺reuptake in human airway smooth muscle

Sathish¹,

Thompson²,

Bailey³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Sarcoplasmic reticulum Ca 2+ ATPases (SERCAs) play a major role in the control of Ca 2+ signalling (Chami et al 2001). Previous experiments F. C. have demonstrated that transfection of SERCA1 increased shortening amplitude and enhanced relaxation kinetics in failing human myocytes (Pieske et al 2002). Interestingly, SERCA1 (Atp2a1) was downregulated in GK rats fed a HFD.…”

Section: Discussionmentioning

confidence: 99%

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Howarth¹,

Qureshi²,

Sobhy³

et al. 2011

Experimental Physiology

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Given the clinical prevalence of type 2 diabetes and obesity and their association with high mortality linked to cardiovascular disease, the aim of the study was to investigate the effects of feeding type 2 diabetic Goto-Kakizaki (GK) rats either high-or low-fat diets on cardiomyocyte structure and function. The GK rats were fed either a high-fat diet (HFD) or a low-fat diet (LFD) from the age of 2 months for a period of 7 months. The GK-HFD rats gained more weight, ate less food and drank less water compared with GK-LFD rats. At 7 months, non-fasting blood glucose was higher in GK-LFD (334 ± 35 mg dl −1 ) compared with GK-HFD rats (235 ± 26 mg dl −1 ). Feeding GK rats with a HFD had no significant effect on glucose clearance following a glucose challenge. Time-to-peak (t peak ) shortening was reduced in myocytes from GK-HFD (131.8 ± 2.1 ms) compared with GK-LFD rats (144.5 ± 3.0 ms), and time-to-half (t 1 /2 ) relaxation of shortening was also reduced in myocytes from GK-HFD (71.7 ± 6.9 ms) compared with GK-LFD rats (86.1 ± 3.6 ms). The HFD had no significant effect on the amplitude of shortening. The HFD had no significant effect on t peak , t 1 /2 decay, amplitude of the Ca 2+ transient, myofilament sensitivity to Ca 2+ , sarcoplasmic reticulum Ca 2+ content, fractional release of Ca 2+ and the rate of Ca 2+ uptake. Structurally, ventricular myocytes from GK-HFD rats showed extensive mitochondrial lesions, including swelling, loss of cristae, and loss of inner and outer membranes, resulting in gross vacuolarization and deformation of ventricular mitochondria with a subsequent reduction in mitochondrial density. Expression of genes encoding various L-type Ca 2+ channel proteins (Cacnb2) and cardiac muscle proteins (Myl2 and Atp2a1) were downregulated in GK-HFD compared with GK-LFD rats. Structural lesions and changed expression of genes encoding various cardiac muscle proteins might partly underlie the altered time course of myocyte shortening and relaxation in myocytes from GK-HFD compared with GK-LFD rats. A variety of diastolic and systolic dysfunctions have been widely reported in type 2 diabetic patients, and the severity of abnormalities depends on the patients' age and the duration of diabetes. Haemodynamic abnormalities include reduced left ventricular ejection fraction, impaired myocardial velocity at early diastole, abnormal relaxation during the early filling phase, prolonged isovolumetric relaxation, lower peak systolic and early diastolic velocity, impaired diastolic relaxation and filling and reduced peak filling rate (von Bibra et al. 2005;Dounis et al. 2006;Markuszewski et al. 2006;Sharman et al. 2007). The GotoKakizaki (GK) rat is a genetic animal model of type 2 diabetes, which was created by selective breeding of an outbred colony of Wistar rats with selection for high

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“…17,18 Contraction of cardiomyocytes is mainly controlled by Ca 2 + entry via L-type Ca 2 + channels and subsequent activation of the RyR, positioned in the SR membrane. 19 RyR, as a SR Ca 2 + release channel, is an essential component of ECC in cardiac contractility and is modulated by several factors such as Ca 2 + , Mg 2 + , and protein kinase A (PKA). 20,21 Further, phospholamban is a phosphoprotein modulating Ca 2 + -ATPase 2a through which ELT (0.3 mg/mL), n = 6; propranolol (1 lM) + ELT (0.3 mg/mL), n = 4; propranolol control, n = 3.…”

Section: Discussionmentioning

confidence: 99%

Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca²⁺Entry and Ca²⁺Release in Beating Rabbit Atria

Cui

et al. 2013

Journal of Medicinal Food

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Lycopus lucidus Turcz has been widely used as a traditional Oriental medicine (TOM) in Korea and China and prescribed for the enhancement of heart function. However, the precise effects have yet to be defined. The purpose of the present study was, therefore, to address whether the ethanol extract of Lycopus lucidus Turcz (ELT) has a positive inotropic effect. ELT-induced changes in atrial mechanical dynamics (pulse pressure, dp/dt, and stroke volume), and cAMP efflux were measured in perfused beating rabbit atria. Three active components, rosmarinic acid, betulinic acid, and oleanolic acid were identified in ELT by high performance liquid chromatography analysis. ELT increased atrial dynamics in a concentration-dependent manner without changes in atrial cAMP levels and cAMP efflux. The ELTinduced positive inotropic effect was blocked by inhibition of the L-type Ca 2 + channels and sarcoplasmic reticulum (SR). Inhibitors of b-adrenoceptors had no effect on the ELT-induced positive inotropic effect. The results suggest that ELT exerts a positive inotropic effect via activation of Ca 2 + entry through L-type Ca 2 + channel and Ca 2 + release from the SR in beating rabbit atria.

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Sarcoplasmic reticulum Ca 2+ load in human heart failure

Cited by 37 publications

References 20 publications

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca²⁺reuptake in human airway smooth muscle

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca²⁺reuptake in human airway smooth muscle

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca²⁺Entry and Ca²⁺Release in Beating Rabbit Atria

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Sarcoplasmic reticulum Ca 2+ load in human heart failure

Cited by 37 publications

References 20 publications

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+reuptake in human airway smooth muscle

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+reuptake in human airway smooth muscle

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca2+Entry and Ca2+Release in Beating Rabbit Atria

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Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca²⁺reuptake in human airway smooth muscle

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca²⁺reuptake in human airway smooth muscle

Ethanol Extract ofLycopus lucidusElicits Positive Inotropic Effect Via Activation of Ca²⁺Entry and Ca²⁺Release in Beating Rabbit Atria