Effect of cardiac A1 adenosine receptor overexpression on sarcoplasmic reticulum function

Zucchi, Riccardo; Cerniway, Rachael J.; Ronca-Testoni, S; Morrison, R. Ray; Ronca, G.; Matherne, G. Paul

doi:10.1016/s0008-6363(01)00471-0

Cited by 23 publications

(17 citation statements)

References 25 publications

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“…After stabilization, hearts were perfused for 10 min (preischemia), and normothermic global ischemia was then produced by interruption of the coronary flow for a period of 20 min in the rat and 12 min in the mouse (ischemia). Although the term ischemia refers to the interruption of blood flow, it is used in the present experiments to refer to the interruption of coronary perfusion of saline solution, consistent with previous reports (5,7,27,41). Previous experiments in the isolated rat heart have shown that a 20-min period of ischemia did not produce irreversible damage (29).…”

Section: Methodssupporting

confidence: 61%

“…These findings indicate that, although both PLB phosphorylation sites are involved in the mechanical recovery after ischemia, Thr 17 appears to play a major role. -ATPase 2 (SERCA2)] and/or in the rate of Ca 2ϩ reuptake by the SR have been described in several species, including rats, mice, dogs and humans, submitted to moderate and reversible injury during cardiac surgery (21,23,41,43). A decrease in the intracellular Ca 2ϩ transient has indeed been described in stunned myocytes isolated from chronically instrumented pigs (18) but was not detected in stunned rat myocytes and ventricular trabeculae or in isolated perfused ferret and dog hearts (5,9,11,18 appears to be normalized before complete recovery of myocardial performance in several species (5, 9, 11) does not necessarily mean that Ca 2ϩ homeostasis is not altered during ischemia and reperfusion.…”

mentioning

confidence: 99%

“…Experimental evidence indicates that the function of the sarcoplasmic reticulum (SR) is altered in both reversible as well as irreversible ischemia-reperfusion injury (21,23,32,41,43). In particular, in the case of myocardial stunning, a decrease in the activity of the SR Ca 2ϩ pump [sarco(endo)plasmic reticulum Ca 2ϩ -ATPase 2 (SERCA2)] and/or in the rate of Ca 2ϩ reuptake by the SR have been described in several species, including rats, mice, dogs and humans, submitted to moderate and reversible injury during cardiac surgery (21,23,41,43). A decrease in the intracellular Ca 2ϩ transient has indeed been described in stunned myocytes isolated from chronically instrumented pigs (18) but was not detected in stunned rat myocytes and ventricular trabeculae or in isolated perfused ferret and dog hearts (5,9,11,18).…”

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confidence: 99%

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Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Said¹,

Vittone²,

Mundiña‐Weilenmann³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Said, M., L. Vittone, C. Mundiñ a-Weilenmann, P. Ferrero, E. G. Kranias, and A. Mattiazzi. Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants. uptake and myocardial contractility and relaxation. In perfused rat hearts submitted to ischemia-reperfusion, we previously showed an ischemia-induced Ser 16 phosphorylation that was dependent on ␤-adrenergic stimulation and an ischemia and reperfusion-induced Thr 17 phosphorylation that was dependent on Ca 2ϩ influx. To elucidate the relationship between these two PLB phosphorylation sites and postischemic mechanical recovery, rat hearts were submitted to ischemiareperfusion in the absence and presence of the CaMKII inhibitor KN-93 (1 M) or the ␤-adrenergic blocker dl-propranolol (1 M). KN-93 diminished the reperfusion-induced Thr 17 phosphorylation and depressed the recovery of contraction and relaxation after ischemia. dl-Propranolol decreased the ischemia-induced Ser 16 phosphorylation but failed to modify the contractile recovery. To obtain further insights into the functional role of the two PLB phosphorylation sites in postischemic mechanical recovery, transgenic mice expressing wild-type PLB (PLB-WT) or PLB mutants in which either Thr 17 or Ser 16 were replaced by Ala (PLB-T17A and PLB-S16A, respectively) into the PLB-null background were used. Both PLB mutants showed a lower contractile recovery than PLB-WT. However, this recovery was significantly impaired all along reperfusion in PLB-T17A, whereas it was depressed only at the beginning of reperfusion in PLB-S16A. Moreover, the recovery of relaxation was delayed in PLB-T17A, whereas it did not change in PLB-S16A, compared with PLB-WT. These findings indicate that, although both PLB phosphorylation sites are involved in the mechanical recovery after ischemia, Thr 17 appears to play a major role. -ATPase 2 (SERCA2)] and/or in the rate of Ca 2ϩ reuptake by the SR have been described in several species, including rats, mice, dogs and humans, submitted to moderate and reversible injury during cardiac surgery (21,23,41,43). A decrease in the intracellular Ca 2ϩ transient has indeed been described in stunned myocytes isolated from chronically instrumented pigs (18) but was not detected in stunned rat myocytes and ventricular trabeculae or in isolated perfused ferret and dog hearts (5,9,11,18 appears to be normalized before complete recovery of myocardial performance in several species (5, 9, 11) does not necessarily mean that Ca 2ϩ homeostasis is not altered during ischemia and reperfusion. There is a compelling body of evidence that indicates that in all species studied, cytosolic Ca 2ϩ concentration rises during ischemia (2,27,31). Furthermore, reperfusion in-

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Section: Methodssupporting

confidence: 61%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Said¹,

Vittone²,

Mundiña‐Weilenmann³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…On the other hand, experimental evidence indicates that the function of the SR is altered both in reversible and irreversible ischemiareperfusion injury (30)(31)(32)(33)(34). In particular, in the case of myocardial stunning, a decrease in the activity of SERCA2a and/or in the rate of Ca 2+ reuptake by the SR has been described in several species (31)(32)(33)(34).…”

Section: Stunningmentioning

confidence: 99%

“…In particular, in the case of myocardial stunning, a decrease in the activity of SERCA2a and/or in the rate of Ca 2+ reuptake by the SR has been described in several species (31)(32)(33)(34). Thus, an obvious question is: why does the intracellular Ca 2+ transient remain unaltered in species in which SR function is depressed?…”

Section: Stunningmentioning

confidence: 99%

The importance of the Thr17 residue of phospholamban as a phosphorylation site under physiological and pathological conditions

Mattiazzi

Mundiña‐Weilenmann

Vittone

et al. 2006

Braz J Med Biol Res

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The sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2a) is under the control of an SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a, whereas phosphorylation of PLN at either the Ser 16 site by PKA or the Thr 17 site by CaMKII reverses this inhibition, thus increasing SERCA2a activity and the rate of Ca 2+ uptake by the SR. This leads to an increase in the velocity of relaxation, SR Ca 2+ load and myocardial contractility. In the intact heart, ß-adrenoceptor stimulation results in phosphorylation of PLN at both Ser 16 and Thr 17 residues. Phosphorylation of the Thr 17 residue requires both stimulation of the CaMKII signaling pathways and inhibition of PP1, the major phosphatase that dephosphorylates PLN. These two prerequisites appear to be fulfilled by ß-adrenoceptor stimulation, which as a result of PKA activation, triggers the activation of CaMKII by increasing intracellular Ca 2+ , and inhibits PP1. Several pathological situations such as ischemia-reperfusion injury or hypercapnic acidosis provide the required conditions for the phosphorylation of the Thr 17 residue of PLN, independently of the increase in PKA activity, i.e., increased intracellular Ca 2+ and acidosis-induced phosphatase inhibition. Our results indicated that PLN was phosphorylated at Thr 17 at the onset of reflow and immediately after hypercapnia was established, and that this phosphorylation contributes to the mechanical recovery after both the ischemic and acidic insults. Studies on transgenic mice with Thr 17 mutated to Ala (PLN-T17A) are consistent with these results. Thus, phosphorylation of the Thr 17 residue of PLN probably participates in a protective mechanism that favors Ca 2+ handling and limits intracellular Ca 2+ overload in pathological situations.

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Mechanisms of cardiac protection with Overexpression of A₁ adenosine receptors

Lankford

Cerniway

Regan

et al. 2003

Drug Development Research

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Myocardial damage from ischemia/reperfusion injury can be minimized through endogenous protective mechanisms, including activation of A 1 adenosine receptors. Transgenic mice with cardiac-specific A 1 adenosine receptor overexpression (A 1 AR Trans) have demonstrated functional and metabolic tolerance to in vitro and in vivo myocardial ischemia/reperfusion injury. The purpose of this investigation is to examine the role of p38 MAP kinase in A 1 receptor-mediated cardioprotection. Activation of p38 MAPK by A 1 adenosine receptor stimulation was evaluated in neonatal rat cardiomyocytes subjected to simulated ischemia. A 1 activation by cyclopentyladenosine decreased cell death and simultaneously enhanced p38 phosphorylation by simulated ischemia. The role of p38 MAP kinase activation in cardioprotection with A 1 adenosine receptor overexpression was evaluated in isolated perfused hearts from A 1 AR Trans mice subjected to 20 min ischemia and 30 min reperfusion. Inhibition of p38 MAPK activity with 10 mM SB-203580 prior to ischemia and during reperfusion decreased postischemic total functional recovery in A 1 AR Trans hearts from 54 7 1 to 2777% of maximal and increased final EDP from 1073 mmHg to 3478 mmHg. A 1 adenosine receptor-mediated activation of p38 MAP kinase in cardiomyocytes is involved in the protection of cells from ischemic death. Tolerance to ischemic injury by A 1 receptor overexpression is dependent upon activation of p38 MAPK. These findings suggest that adenosine A 1 mediated cardioprotection in transgenic mice involves activation of the p38 MAP kinase cascade. Drug Dev.

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Effect of cardiac A1 adenosine receptor overexpression on sarcoplasmic reticulum function

Cited by 23 publications

References 25 publications

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

The importance of the Thr17 residue of phospholamban as a phosphorylation site under physiological and pathological conditions

Mechanisms of cardiac protection with Overexpression of A₁ adenosine receptors

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Effect of cardiac A1 adenosine receptor overexpression on sarcoplasmic reticulum function

Cited by 23 publications

References 25 publications

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

The importance of the Thr17 residue of phospholamban as a phosphorylation site under physiological and pathological conditions

Mechanisms of cardiac protection with Overexpression of A1 adenosine receptors

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Product

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About

Mechanisms of cardiac protection with Overexpression of A₁ adenosine receptors