Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats

Romero‐García, Tatiana; Landa-Galván, Huguet V.; Pavón, Natalia; Mercado-Morales, Martha; Valdivia, Héctor H.; Rueda, Angélica

doi:10.1016/j.ceca.2020.102267

Cited by 5 publications

(13 citation statements)

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“…In cardiomyocytes from C57BL/6J or DBA/1 mouse, the expression of PLB was equivalent (Figure 5a,b). The activation of PLB is regulated by cAMP‐induced PKA and calcium‐induced kinases especially Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII), which is closely related to the intracellular level of Ca 2+ (Romero‐García et al., 2020). To identify the activity of both factors in cardiomyocytes of C57BL/6J and DBA/1 mice, we detected the phosphorylation of PLB at the serine‐16 site (a PKA‐dependent site, Figure 5a) and the threonine‐17 site (a Ca 2+ /CaM‐dependent site, Figure 5b) (Zhong et al., 2017).…”

Section: Resultsmentioning

confidence: 99%

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

Wang

Zhou

Guo

et al. 2021

Experimental Physiology

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Cardiovascular mortality has been increasing, and in particular, cardiovascular damage caused by some chronic autoimmune diseases accounts for a large proportion of this. C57BL/6J mice have been used mostly in studies of cardiovascular diseases. However, for purposes of modelling, this strain of mouse has a very low incidence of some chronic immune diseases such as rheumatoid arthritis, to which instead DBA/1 mice are more susceptible. Basic cardiac function differs between mice with different genetic backgrounds. Therefore, we monitored cardiac function and structure of normal male C57BL/6J and DBA/1 mice for six consecutive months. Echocardiography was used to monitor cardiac functions once a month and cardiac systolic function was measured upon isoproterenol challenge at the end of observation. The Excitationcontraction coupling-related proteins were measured by western blotting. Heart tissue sections were subject to haematoxylin-eosin, TUNEL and Alizarin red staining. The results demonstrated that systolic and diastolic function did not vary significantly and both strains were indistinguishable in appearance and structure of hearts. DBA/1 mice showed a good cardiac β-adrenergic response comparable to C57BL/6J mice with isoproterenol treatment. The phosphorylation of phospholamban at either its protein kinase A or its Ca 2+ /calmodulin-dependent protein kinase II site, as well as the activation of troponin I showed no significant difference between strains. These findings suggested that there was no obvious difference in the heart structure and function of normal male DBA/1 mice compared with C57BL/6J mice. The DBA/1 mouse is a strain applicable to investigating autoimmune disease-induced heart dysfunction and exploring potential interventions.

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Section: Resultsmentioning

confidence: 99%

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

Wang

Zhou

Guo

et al. 2021

Experimental Physiology

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“…The research reviewed above suggests that both PKA and CaMKII-δ play important roles in β 1 -AR-mediated responses and that alterations in the expression or function of these kinases can therefore be deleterious. Moreover, enhanced and sustained β-adrenergic stimulation contributes to the development of such pathological conditions as HF[ 29 ]; these alterations may also extend to diabetic and pre-diabetic cardiomyopathy[ 28 , 35 , 48 ]. A recent study showed that incubation of isolated mouse cardiomyocytes in high extracellular glucose (30 mmol/L) to mimic acute hyperglycemia leads to O-GlcNAcylation at CaMKII Ser 280 and enhanced kinase activity, resulting in RyR2 phosphorylation and pro-arrhythmogenic activity[ 45 ].…”

Section: β-Adrenergic Receptor Signaling In the Heart: Pka And Camkii Activationmentioning

confidence: 99%

“…Importantly, despite the discrepancies in metabolic alterations all these animal models developed pre-diabetic cardiomyopathy, characterized by several cardiac alterations. For instance, increased heart rate was reported in five models[ 27 , 48 , 51 , 56 , 63 ]; however, other studies in which this parameter was evaluated did not report changes[ 60 , 62 , 65 , 66 ]. Systolic dysfunction has also been observed, including decreased heart contractility, ventricular pressure, and intracellular Ca 2+ transient amplitude[ 27 , 55 , 60 , 67 - 71 ], along with reduced fractional shortening[ 55 , 65 - 67 , 70 - 72 ] (Table 1 ).…”

Section: Animal Models Of Pre-diabetic Cardiomyopathymentioning

confidence: 99%

“…Systolic dysfunction has also been observed, including decreased heart contractility, ventricular pressure, and intracellular Ca 2+ transient amplitude[ 27 , 55 , 60 , 67 - 71 ], along with reduced fractional shortening[ 55 , 65 - 67 , 70 - 72 ] (Table 1 ). Diastolic dysfunction is also manifested by increased diastolic Ca 2+ leak in the form of Ca 2+ waves, without altering cytoplasmic Ca 2+ levels[ 48 , 55 , 62 ]. To compensate for compromised cardiac output, the heart grows; however, few studies have documented either heart hypertrophy[ 27 , 55 , 66 ] or left ventricle hypertrophy[ 55 , 71 ].…”

Section: Animal Models Of Pre-diabetic Cardiomyopathymentioning

confidence: 99%

“…To compensate for compromised cardiac output, the heart grows; however, few studies have documented either heart hypertrophy[ 27 , 55 , 66 ] or left ventricle hypertrophy[ 55 , 71 ]. Interestingly, several pre-diabetic cardiomyopathy models develop increased aortic pressure[ 27 , 28 , 51 , 73 ] and high arrhythmia incidence under basal or stressful conditions[ 48 , 55 , 56 , 63 ] (Table 1 ). Of note, rats and mice are the most common animal models for inducing pre-diabetic cardiomyopathy, although pigs and dogs have also been employed because of their greater degree of similarity to human cardiac physiology, including ionic currents that contribute to the cardiac action potential[ 74 ], Ca 2+ removal mechanisms, and ECC regulatory mechanisms[ 19 ].…”

Section: Animal Models Of Pre-diabetic Cardiomyopathymentioning

confidence: 99%

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Tale of two kinases: Protein kinase A and Ca²⁺/calmodulin-dependent protein kinase II in pre-diabetic cardiomyopathy

Gaitán-González

Sánchez-Hernández

Arias‐Montaño

et al. 2021

WJD

Self Cite

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Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations, including insulin resistance, visceral fat accumulation, and dyslipidemias, which increase the risk for developing cardiovascular disease. Metabolic syndrome is associated with augmented sympathetic tone, which could account for the etiology of pre-diabetic cardiomyopathy. This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustained β-adrenergic response in pre-diabetes, focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy. The research reviewed indicates that both protein kinase A and Ca 2+ /calmodulin-dependent protein kinase II play important roles in functional responses mediated by β 1 -adrenoceptors; therefore, alterations in the expression or function of these kinases can be deleterious. This review also outlines recent information on the role of protein kinase A and Ca 2+ /calmodulin-dependent protein kinase II in abnormal Ca 2+ handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.

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Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy

Giusti

Palomeque

Mattiazzi

2022

Pflugers Arch - Eur J Physiol

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Diabetic cardiomyopathy is defined as the myocardial dysfunction that suffers patients with diabetes mellitus (DM) in the absence of hypertension and structural heart diseases such as valvular or coronary artery dysfunctions. Since the impact of DM on cardiac function is rather silent and slow, early stages of diabetic cardiomyopathy, known as prediabetes, are poorly recognized, and, on many occasions, cardiac illness is diagnosed only after a severe degree of dysfunction was reached. Therefore, exploration and recognition of the initial pathophysiological mechanisms that lead to cardiac dysfunction in diabetic cardiomyopathy are of vital importance for an on-time diagnosis and treatment of the malady. Among the complex and intricate mechanisms involved in diabetic cardiomyopathy, Ca 2+ mishandling and mitochondrial dysfunction have been described as pivotal early processes. In the present review, we will focus on these two processes and the molecular pathway that relates these two alterations to the earlier stages and the development of diabetic cardiomyopathy. Supplementary Information The online version contains supplementary material available at 10.1007/s00424-021-02650-y.

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Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats

Cited by 5 publications

References 65 publications

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

Tale of two kinases: Protein kinase A and Ca²⁺/calmodulin-dependent protein kinase II in pre-diabetic cardiomyopathy

Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy

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Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats

Cited by 5 publications

References 65 publications

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

Tale of two kinases: Protein kinase A and Ca2+/calmodulin-dependent protein kinase II in pre-diabetic cardiomyopathy

Ca2+ mishandling and mitochondrial dysfunction: a converging road to prediabetic and diabetic cardiomyopathy

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Tale of two kinases: Protein kinase A and Ca²⁺/calmodulin-dependent protein kinase II in pre-diabetic cardiomyopathy