The role of protein kinases and protein phosphatases in the regulation of cardiac sarcoplasmic reticulum function

Kranias, Evangelia G.; Gupta, Ramesh C.; Jakab, G; Kim, Hae Won; Steenaart, Nancy A. E.; Rapundalo, Stephen T.

doi:10.1007/bf00242513

Cited by 24 publications

(16 citation statements)

References 16 publications

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“…It is well established that Ca 2ϩ entry into pancreatic ␤-cells stimulates insulin secretion and that CaMKII activity influences Ca 2ϩ homeostasis in many cell types (20,(33)(34)(35). Although CaMKII has been implicated in regulating islet insulin secretion, mechanisms underlying CaMKII action in ␤-cells are poorly understood (2).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Pancreatic β-Cell Ca2+/Calmodulin-dependent Protein Kinase II Reduces Glucose-stimulated Calcium Influx and Insulin Secretion, Impairing Glucose Tolerance

Dadi

Vierra

Ustione

et al. 2014

Journal of Biological Chemistry

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Background: Glucose activates CaMKII in ␤-cells, how this influences glucose homeostasis has not been determined. Results: Inhibiting CaMKII in mouse ␤-cells causes glucose intolerance by reducing Ca 2ϩ entry and insulin secretion. Conclusion: CaMKII is a ␤-cell Ca 2ϩ sensor that amplifies secretagogue-induced Ca 2ϩ entry and insulin secretion to maintain glucose homeostasis. Significance: This provides the first evidence that ␤-cell CaMKII modulates glucose homeostasis under physiological and insulin resistant states.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Pancreatic β-Cell Ca2+/Calmodulin-dependent Protein Kinase II Reduces Glucose-stimulated Calcium Influx and Insulin Secretion, Impairing Glucose Tolerance

Dadi

Vierra

Ustione

et al. 2014

Journal of Biological Chemistry

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“…30 Until now, studies of this kind have been restricted to nonhypertensive, nonhypertrophic models. Our data suggest, however, that the adverse effect of diabetes on left ventricular SR calcium uptake activity is exacerbated by preexisting LVH (Figure 3, Table 5).…”

Section: Discussionmentioning

confidence: 99%

Ventricular relaxation of diabetic spontaneously hypertensive rat.

1990

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Diabetes, and possibly the hypothyroidism that attends diabetes, impairs mechanical relaxation of ventricular muscle, in part by depressing the rate of Ca 2+ uptake by sarcoplasmic reticulum. Left ventricular hypertrophy exacerbates the adverse effects of diabetes on cardiac performance, but its effects on relaxation variables have not been well characterized. We examined the impact of streptozotocin-induced diabetes (8 weeks) on ventricular pressure load-dependent relaxation and sarcoplasmic reticular calcium uptake of hearts from spontaneously hypertensive rats and Wistar-Kyoto rats. Subsets of diabetic hypertensive rats were treated with either insulin (10 units/kg/day) or triiodothyronine (8-10 /tg/kg/day). Diabetes impaired load-dependent relaxation and depressed sarcoplasmic reticular calcium uptake only in spontaneously hypertensive rat hearts. Either insulin or triiodothyronine treatment prevented the diabetes-induced depressions of both mechanical and biochemical indexes of relaxation. The results suggest that 1) hypertrophic ventricles of spontaneously hypertensive rats are more susceptible to the detrimental effects of diabetes on relaxation indexes than are the nonhypertrophic Wistar-Kyoto rat ventricles, and 2) the hypothyroidism that attends diabetes may contribute to the impaired relaxation of diabetic spontaneously hypertensive rat left ventricle. have an impact on ventricular relaxation. The presence of LVH alone may or may not be associated with impaired relaxation. "17 However, when diabetes coexists with LVH in the spontaneously hypertensive rat (SHR), the rate of left ventricular pressure decline of perfused hearts is more profoundly depressed when compared with the effects of diabetes in normotensive rat strains. -13 Isometric relaxation is also prolonged in hypertrophic papillary muscles from the diabetic renovascular hypertensive rat.12 These results would suggest that combined effects of diabetes and LVH on SR Ca 2+ uptake might be more pronounced than the influence of either condition individually. However, the interaction between diabetes and LVH on the relation between myocardial relaxation and SR calcium uptake has not been characterized.Reduced serum levels of thyroid hormones are often associated with diabetes, l *-n and this hypothyroidism (or "low thyroid state") may contribute to diabetic cardiomyopathy. Thyroid hormone deficiencies, like diabetes, can lead to prolonged relaxation and depressed rates of SR calcium uptake in the myocardium. 18- 19 The effects of hypothyroidism on these measurements are well correlated, both in nonhypertrophic and hypertrophic ventricles. 20 Treatment of the diabetic SHR with triiodothyronine (T 3 ) effectively prevents the resultant cardiac dysfunction, 21 -22 but the influence of T 3 treatment in nonhypertensive diabetic rat models is inconsistent.

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“…In vitro studies demonstrated that Ser 16 is phosphorylated by cAMP-dependent protein kinase (PKA) and Thr 17 by Ca 2+ -calmodulin-(CaM-) dependent protein kinase (CaM kinase II, [15,30]). PKA-dependent phosphorylation of Ser 16 -PLB increases the Ca 2+ sensitivity of SERCA 2a [24,29], whereas CaM-kinase dependent phosphorylation of Thr 17 -PLB increases the Vmax of SERCA 2a. It was reported that Ser 16 -phosphorylation of PLB is a prerequisite for the CaM-kinase dependent Thr 17 -phosphorylation of PLB [17].…”

Section: Introductionmentioning

confidence: 97%

“…Phosphorylation of PLB removes its inhibitory effects on SERCA 2a, thereby accelerating Ca 2+ uptake and cardiac relaxation [9,16,30]. In response to β-adrenergic stimulation in vivo, PLB is phosphorylated at two adjacent amino acids, Ser 16 and Thr 17 [35]. In vitro studies demonstrated that Ser 16 is phosphorylated by cAMP-dependent protein kinase (PKA) and Thr 17 by Ca 2+ -calmodulin-(CaM-) dependent protein kinase (CaM kinase II, [15,30]).…”

Section: Introductionmentioning

confidence: 99%

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Ser 16 -, but not Thr 17 -phosphorylation of phospholamban influences frequency-dependent force generation in human myocardium

Brixius

Wollmer

Bölck

et al. 2003

Pfl�gers Archiv European Journal of Physiology

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Beta-adrenoceptor/cAMP-dependent Ser16-phosphorylation as well as Ca(2+)-dependent Thr17-phosphorylation of phospholamban (PLB) influences SERCA 2a activity and thus myocardial contractility. To determine the cross-signaling between Ca2+ and cAMP pathways, the phosphorylation of Ser16-PLB and Thr17-PLB was studied at increasing stimulation frequencies as well as in the presence of beta-adrenergic stimulation in isolated ventricular trabeculae from failing (dilative cardiomyopathy, DCM, heart transplants, n=9) and non-failing human myocardium (donor hearts, NF, n=9). In addition, we measured the intracellular Ca(2+)-transient (fura-2) at increasing stimulation frequencies (0.5-3.0 Hz). Protein expression of SERCA 2a and phospholamban was similar in DCM and NF. In DCM, diastolic [Ca2+]i was increased and systolic [Ca2+]i as well as Ser16 PLB-phosphorylation were decreased as compared to NF at 0.5 Hz. The positive force-frequency relationship in human non-failing myocardium was accompanied by a frequency-dependent increase in Ser16-PLB, but not Thr17-PLB phosphorylation. In DCM, Ser16-PLB as well as Thr17-PLB phosphorylation were not altered at higher stimulation frequencies. After application of isoprenaline (1 microM), a profound increase in Ser16-PLB phosphorylation was accompanied by a small increase in Thr17-PLB phosphorylation, only in NF. The frequency-dependent phosphorylation of Ser16-PLB may favor an increase in Ca2+ transient and force generation in humans. Cross talk signaling of Ser16/Thr17-PLB phosphorylation after beta-adrenergic stimulation exists in non-failing, but not in failing human myocardium. The Ca(2+)-dependent CaM-kinase activity may be altered in human heart failure.

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The role of protein kinases and protein phosphatases in the regulation of cardiac sarcoplasmic reticulum function

Cited by 24 publications

References 16 publications

Inhibition of Pancreatic β-Cell Ca2+/Calmodulin-dependent Protein Kinase II Reduces Glucose-stimulated Calcium Influx and Insulin Secretion, Impairing Glucose Tolerance

Inhibition of Pancreatic β-Cell Ca2+/Calmodulin-dependent Protein Kinase II Reduces Glucose-stimulated Calcium Influx and Insulin Secretion, Impairing Glucose Tolerance

Ventricular relaxation of diabetic spontaneously hypertensive rat.

Ser 16 -, but not Thr 17 -phosphorylation of phospholamban influences frequency-dependent force generation in human myocardium

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