Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart

Temsah, Rana M.; Netticadan, Thomas; Chapman, Donald; Takeda, Satoshi; Mochizuki, Seibu; Dhalla, Naranjan S.

doi:10.1152/ajpheart.1999.277.2.h584

Cited by 108 publications

(181 citation statements)

References 24 publications

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“…Western blot analyses-Protocols described in reference 18 were followed [18]. Protein samples (120 μg of total protein per lane) were separated by 5% SDS-PAGE gels for RyR and transferred to PVDF membranes.…”

Section: 24mentioning

confidence: 99%

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

Fu¹,

Li²,

Fan³

et al. 2008

Biochemical Pharmacology

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The present study established a model of RyR 2 knockdown cardiomyocytes and elucidated the role of RyR 2 in aconitine-induced arrhythmia. Cardiomyocytes were obtained from hearts of neonatal Sprague-Dawlay rats. siRNAs were used to down-regulate RyR 2 expression. Reduction of RyR 2 expression was documented by RT-PCR, western blot, and immunofluorescence. Ca 2+ signals were investigated by measuring the relative intracellular Ca 2+ concentration, spontaneous Ca 2+ oscillations, caffeine-induced Ca 2+ release, and L-type Ca 2+ currents. In normal cardiomyocytes, steady and periodic spontaneous Ca 2+ oscillations were observed, and the baseline [Ca 2+ ] i remained at the low level. Exposure to 3 μM aconitine increased the frequency and decreased the amplitude of Ca 2+ oscillations; the baseline [Ca 2+ ] i and the level of caffeineinduced Ca 2+ release were increased but the L-type Ca 2+ currents were inhibited after application of 3 μM aconitine for 5 min. In RyR 2 knockdown cardiomyocytes, the steady and periodic spontaneous Ca 2+ oscillations almost disappeared, but were re-induced by aconitine without affecting the baseline [Ca 2+ ] i level; the level of caffeine-induced Ca 2+ release was increased but L-type Ca 2+ currents were inhibited. Alterations of RyR 2 are important consequences of aconitinestimulation and activation of RyR 2 appear to have a direct relationship with aconitine-induced arrhythmias. The present study demonstrates a potential method for preventing aconitine-induced arrhythmias by inhibiting Ca 2+ leakage through the sarcoplasmic reticulum RyR 2 channel.

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Section: 24mentioning

confidence: 99%

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

Fu¹,

Li²,

Fan³

et al. 2008

Biochemical Pharmacology

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“…38 Probes for SERCA-2, phospholamban, ryanodine receptor calsequestrin (from rabbit heart), and glyceraldehyde-3 phosphate dehydrogenase (GAPDH) were 523, 2090, 535, 2400, and 428 bp, respectively.…”

Section: Ca 2+ -Regulatory Proteinsmentioning

confidence: 99%

Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling

et al. 2005

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The serine-threonine kinase Akt/PKB mediates stimuli from different classes of cardiomyocyte receptors, including the growth hormone/insulin like growth factor and the b-adrenergic receptors. Whereas the growth-promoting and antiapoptotic properties of Akt activation are well established, little is known about the effects of Akt on myocardial contractility, intracellular calcium (Ca 2+ ) handling, oxygen consumption, and b-adrenergic pathway. To this aim, Sprague-Dawley rats were subjected to a wild-type Akt in vivo adenoviral gene transfer using a catheter-based technique combined with aortopulmonary crossclamping. Left ventricular (LV) contractility and intracellular Ca 2+ handling were evaluated in an isolated isovolumic bufferperfused, aequorin-loaded whole heart preparations 10 days after the surgery. The Ca 2+ -force relationship was obtained under steady-state conditions in tetanized muscles. No significant hypertrophy was detected in adenovirus with wild-type Akt (Ad.Akt) versus controls rats (LV-to-body weight ratio 2.670.2 versus 2.770.1 mg/g, controls versus Ad.Akt, P, NS). LV contractility, measured as developed pressure, increased by 41% in Ad.Akt. This was accounted for by both more systolic Ca 2+ available to the contractile machinery (+19% versus controls) and by enhanced myofilament Ca 2+ responsiveness, documented by an increased maximal Ca 2+ -activated pressure (+19% versus controls) and a shift to the left of the Ca 2+ -force relationship. Such increased contractility was paralleled by a slight increase of myocardial oxygen consumption (14%), while titrated dose of dobutamine providing similar inotropic effect augmented oxygen consumption by 39% (Po0.01). Phospholamban, calsequestrin, and ryanodine receptor LV mRNA and protein content were not different among the study groups, while sarcoplasmic reticulum Ca 2+ ATPase protein levels were significantly increased in Ad.Akt rats. b-Adrenergic receptor density, affinity, kinase-1 levels, and adenylyl cyclase activity were similar in the three animal groups. In conclusion, our results support an important role for Akt/PKB in the regulation of myocardial contractility and mechanoenergetics.

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“…Beta-adrenoceptor blockers are believed to have some direct effects on the myocardial membrane, 13,19 antiperoxidative activity, 10 antiradical effect, 20 sarcoplasmic reticular (SR) function, 14 and cardiac SR gene expression. 14 Propranolol, a non-specific ß-adrenoceptor blocker, has been reported to have a cardioprotective effect via several actions, such as membrane-stabilizing activity 13 and inhibition of the enzyme NADH oxidase, 21 and/or higher lipophilic property.…”

Section: Discussionmentioning

confidence: 99%

Landiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts

Kurosawa

Kanaya

Niiyama

et al. 2003

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : Beta blockers are thought to exert beneficial effects on the ischemic heart. The authors examined the effects of landiolol (ONO 1101), a highly selective ß1 antagonist, propranolol, a nonspecific ß blocker, and esmolol, a selective ß1 antagonist, on postischemic contractile recovery. Drugs were given prophylactically.M Me et th ho od ds s: : Ischemia-reperfusion in isolated guinea pig hearts was induced by stopping the perfusion for 45 min and reperfusing for 60 min. Hearts (n = 7 in each group) were treated with or without propranolol (1 or 10 µM), esmolol (5 or 50 µM), or landiolol (20, 100 or 500 µM) ten minutes before inducing ischemia.R Re es su ul lt ts s: : At the end of reperfusion, left ventricular pressure (LVP) recovered to 64 ± 3% of the baseline value in the control group. With 1 and 10 µM propranolol, LVP recovered to 90 ± 5% and 100 ± 6% of the baseline value at 60 min after reperfusion, respectively. Fifty µM but not 5 µM of esmolol resulted in restoration of LVP to 97 ± 17% of the pre-ischemic value at 60 min after reperfusion. In hearts pretreated with 100 and 500 µM landiolol, LVP was restored to 109 ± 5% and 104 ± 5% of the baseline value, respectively. Landiolol 100 µM did not depress LVP in the pre-ischemic period.C Co on nc cl lu us si io on ns s: : The present study shows that landiolol, an ultrashort-acting cardioselective ß1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three ß blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period. Objectif Méthode : L'ischémie-reperfusion a été induite dans des coeurs de cobaye isolés en stoppant la perfusion pendant 45 min et en reperfusant pendant 60 min. Les coeurs (n = 7 dans chaque groupe) ont été traités avec ou sans propranolol (1 ou 10 µM), esmolol (5 ou 50 µM) ou landiolol (20, 100 ou 500 µM) dix minutes avant l'induction de l'ischémie. Résultats

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Alterations in sarcoplasmic reticulum function and gene expression in ischemic-reperfused rat heart

Cited by 108 publications

References 24 publications

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

Sarcoplasmic reticulum Ca2+ release channel ryanodine receptor (RyR2) plays a crucial role in aconitine-induced arrhythmias

Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling

Landiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts

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