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Obesity does not lead to imbalance between myocardial phospholamban phosphorylation and dephosphorylation.

Freire PP, Alves CA, Deus AF, Leopoldo AP, Leopoldo AS, Silva DC, Tomasi LC, Campos DH, Cicogna AC - Arq. Bras. Cardiol. (2014)

Bottom Line: In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation.Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16.Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil.

ABSTRACT

Background: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA.

Objective: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation.

Methods: Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot.

Results: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16.

Conclusion: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

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Related in: MedlinePlus

A. The prevalence of phosphorylation occurs when PKA is activated while itphosphorylates I-1, thus preventing PLB dephosphorylation. B. The prevalenceof dephosphorylation occurs when PKA is not activated. There is no PLB andI-1 phoshporylation, therefore PP-1 maintains its active state. cAMP: 3’5’cyclic adenosine monophosphate; I-1: inhibitory protein 1; P: phosphate;PKA: protein kinase A; pPLB: phosphorylated phospholamban; PLB:dephosphorylated phospholamban; PP-1: phosphatase-1; Serca2a:Ca2+ pump.
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f02: A. The prevalence of phosphorylation occurs when PKA is activated while itphosphorylates I-1, thus preventing PLB dephosphorylation. B. The prevalenceof dephosphorylation occurs when PKA is not activated. There is no PLB andI-1 phoshporylation, therefore PP-1 maintains its active state. cAMP: 3’5’cyclic adenosine monophosphate; I-1: inhibitory protein 1; P: phosphate;PKA: protein kinase A; pPLB: phosphorylated phospholamban; PLB:dephosphorylated phospholamban; PP-1: phosphatase-1; Serca2a:Ca2+ pump.

Mentions: The connection PLB-SERCA2a is controlled by cycles of phosphorylation anddephosphorylation, by the action of PKA and phosphatase 1 (PP-1), respectively. Theprevalence of PLB phosphorylation, site of serine 16, occurs with the activation ofPKA. Simultaneously, phosphorylates the inhibitory protein (I-1), thus forming thecomplex I-1/PP-1 and preventing PLB dephosphorylation caused by PP-1.Dephosphorylation is prevalent when PKA is deactivated, therefore there is no PLBand I-1 phosphorylation; when phosphate is not added to I-1, the formation ofI-1/PP-1 is not possible, which allows PP-1 to dephosphorylate PLB, in its activestate6-8 (Figure2).


Obesity does not lead to imbalance between myocardial phospholamban phosphorylation and dephosphorylation.

Freire PP, Alves CA, Deus AF, Leopoldo AP, Leopoldo AS, Silva DC, Tomasi LC, Campos DH, Cicogna AC - Arq. Bras. Cardiol. (2014)

A. The prevalence of phosphorylation occurs when PKA is activated while itphosphorylates I-1, thus preventing PLB dephosphorylation. B. The prevalenceof dephosphorylation occurs when PKA is not activated. There is no PLB andI-1 phoshporylation, therefore PP-1 maintains its active state. cAMP: 3’5’cyclic adenosine monophosphate; I-1: inhibitory protein 1; P: phosphate;PKA: protein kinase A; pPLB: phosphorylated phospholamban; PLB:dephosphorylated phospholamban; PP-1: phosphatase-1; Serca2a:Ca2+ pump.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126760&req=5

f02: A. The prevalence of phosphorylation occurs when PKA is activated while itphosphorylates I-1, thus preventing PLB dephosphorylation. B. The prevalenceof dephosphorylation occurs when PKA is not activated. There is no PLB andI-1 phoshporylation, therefore PP-1 maintains its active state. cAMP: 3’5’cyclic adenosine monophosphate; I-1: inhibitory protein 1; P: phosphate;PKA: protein kinase A; pPLB: phosphorylated phospholamban; PLB:dephosphorylated phospholamban; PP-1: phosphatase-1; Serca2a:Ca2+ pump.
Mentions: The connection PLB-SERCA2a is controlled by cycles of phosphorylation anddephosphorylation, by the action of PKA and phosphatase 1 (PP-1), respectively. Theprevalence of PLB phosphorylation, site of serine 16, occurs with the activation ofPKA. Simultaneously, phosphorylates the inhibitory protein (I-1), thus forming thecomplex I-1/PP-1 and preventing PLB dephosphorylation caused by PP-1.Dephosphorylation is prevalent when PKA is deactivated, therefore there is no PLBand I-1 phosphorylation; when phosphate is not added to I-1, the formation ofI-1/PP-1 is not possible, which allows PP-1 to dephosphorylate PLB, in its activestate6-8 (Figure2).

Bottom Line: In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation.Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16.Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Clínica Médica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, SP, Brazil.

ABSTRACT

Background: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA.

Objective: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation.

Methods: Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot.

Results: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16.

Conclusion: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system.

Show MeSH
Related in: MedlinePlus