The Physiological and Pathological Roles of Mitochondrial Calcium Uptake in Heart

Lai, Lo; Qiu, Hongyu

doi:10.3390/ijms21207689

Cited by 19 publications

(6 citation statements)

References 96 publications

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“…The heart is one of the highest energy-demanding organs with a high number of mitochondria essential to produce ATP and ensure cardiac contraction. Nevertheless, these important organelles are also the main sources of ROS, whose altered handling can cause their accumulation and therefore triggers detrimental effects on mitochondria themselves and other cell components thus leading to apoptosis and cardiac diseases [ 358 , 359 ].…”

Section: Discussionmentioning

confidence: 99%

The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

Bevere

Morabito

Guarnieri

2022

Oxidative Medicine and Cellular Longevity

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This review is aimed at providing an overview of the key hallmarks of cardiomyocytes in physiological and pathological conditions. The main feature of cardiac tissue is the force generation through contraction. This process requires a conspicuous energy demand and therefore an active metabolism. The cardiac tissue is rich of mitochondria, the powerhouses in cells. These organelles, producing ATP, are also the main sources of ROS whose altered handling can cause their accumulation and therefore triggers detrimental effects on mitochondria themselves and other cell components thus leading to apoptosis and cardiac diseases. This review highlights the metabolic aspects of cardiomyocytes and wanders through the main systems of these cells: (a) the unique structural organization (such as different protein complexes represented by contractile, regulatory, and structural proteins); (b) the homeostasis of intracellular Ca2+ that represents a crucial ion for cardiac functions and E-C coupling; and (c) the balance of Zn2+, an ion with a crucial impact on the cardiovascular system. Although each system seems to be independent and finely controlled, the contractile proteins, intracellular Ca2+ homeostasis, and intracellular Zn2+ signals are strongly linked to each other by the intracellular ROS management in a fascinating way to form a “functional tetrad” which ensures the proper functioning of the myocardium. Nevertheless, if ROS balance is not properly handled, one or more of these components could be altered resulting in deleterious effects leading to an unbalance of this “tetrad” and promoting cardiovascular diseases. In conclusion, this “functional tetrad” is proposed as a complex network that communicates continuously in the cardiomyocytes and can drive the switch from physiological to pathological conditions in the heart.

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Section: Discussionmentioning

confidence: 99%

The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

Bevere

Morabito

Guarnieri

2022

Oxidative Medicine and Cellular Longevity

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“…It is accepted that determination of LDH and CK activity provides one of the biochemical indexes for the evaluation and diagnosis of heart disease, due to the level of LDH in serum reflecting injury in the permeability of the cardiomyocytes, and the activity level of CK being directly related to the consumption and supply of myocardial oxygen and energy, muscle contraction, and mitochondrial function ( Agress, 1965 ; Matschke et al, 2005 ; Ingwall, 2009 ; Zervou et al, 2016 ; Bak and Schousboe, 2017 ; Klein et al, 2020 ). Furthermore, the mitochondrial membrane potential and the intensity of calcium fluorescence, which were testing indexes in the present study, play an essential role in the mitochondrial function of myocardial tissue homeostasis ( Skarka and Ostadal, 2002 ; Dibb et al, 2007 ; Kadenbach et al, 2011 ; Davlouros et al, 2016 ; Zorova et al, 2018 ; Schartner et al, 2019 ; Lai and Qiu, 2020 ). Understanding of the electrophysiological effects in cardiomyocyte contractile and mechanical function in response to cardiotoxic drugs has previously relied on primary cardiomyocytes from animal models ( Liu et al, 2012 ; Tang et al, 2016 ; Blair and Pruitt, 2020 ).…”

Section: Discussionmentioning

confidence: 82%

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research

Zhang

Lü²,

Ren³

et al. 2022

Front. Pharmacol.

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Background: Euodiae Fructus, a well-known herbal medicine, is widely used in Asia and has also gained in popularity in Western countries over the last decades. It has known side effects, which have been observed in clinical settings, but few studies have reported on its cardiotoxicity.Methods: In the present study, experiments using techniques of untargeted metabolomics clarify the hazardous effects of Euodiae Fructus on cardiac function and metabolism in rats in situations of overdosage and unsuitable syndrome differentiation. In vitro assays are conducted to observe the toxic effects of evodiamine and rutaecarpine, two main chemical constituents of Euodiae Fructus, in H9c2 and neonatal rat cardiomyocytes (NRCMs), with their signaling mechanisms analyzed accordingly.Results: The cardiac cytotoxicity of evodiamine and rutaecarpine in in vivo experiments is associated with remarkable alterations in lactate dehydrogenase, creatine kinase, and mitochondrial membrane potential; also with increased intensity of calcium fluorescence, decreased protein expression of the cGMP-PKG pathway in H9c2 cells, and frequency of spontaneous beat in NRCMs. Additionally, the results in rats with Yin deficiency receiving a high-dosage of Euodiae Fructus suggest obvious cardiac physiological dysfunction, abnormal electrocardiogram, pathological injuries, and decreased expression of PKG protein. At the level of endogenous metabolites, the cardiac side effects of overdose and irrational usage of Euodiae Fructus relate to 34 differential metabolites and 10 metabolic pathways involving among others, the purine metabolism, the glycerophospholipid metabolism, the glycerolipid metabolism, and the sphingolipid metabolism.Conclusion: These findings shed new light on the cardiotoxicity induced by Euodiae Fructus, which might be associated with overdose and unsuitable syndrome differentiation, that comes from modulating the cGMP-PKG pathway and disturbing the metabolic pathways of purine, lipid, and amino acid. Continuing research is needed to ensure pharmacovigilance for the safe administration of Chinese herbs in the future.

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“…In cultured human cardiomyocytes, Tat increased [Ca 2+ ] i demonstrating its capacity to exert acute effects on ion flux in heart cells. These findings have been demonstrated to be responsible for changes in cardiac contractility and dysfunction [ 69 , 70 ]. Although the tat transgene was detected in the atrium and ventricular chambers of the heart in Tat(+) mice, we did not observe an overall significant change in cardiac function.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Tat Upregulates the Receptor for Advanced Glycation End Products and Superoxide Dismutase-2 in the Heart of Transgenic Mice

Qrareya

Wise

Hodges

et al. 2022

Viruses

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Cardiovascular disorder (CVD) is a common comorbidity in people living with HIV (PLWH). Although the underlying mechanisms are unknown, virotoxic HIV proteins, such as the trans-activator of transcription (Tat), likely contribute to CVD pathogenesis. Tat expression in mouse myocardium has been found to induce cardiac dysfunction and increase markers of endothelial toxicity. However, the role that Tat may play in the development of CVD pathogenesis is unclear. The capacity for Tat to impact cardiac function was assessed using AC16 human cardiomyocyte cells and adult male and female transgenic mice that conditionally expressed Tat [Tat(+)], or did not [Tat(−)]. In AC16 cardiomyocytes, Tat increased intracellular calcium. In Tat(+) mice, Tat expression was detected in both atrial and ventricular heart tissue. Tat(+) mice demonstrated an increased expression of the receptor for advanced glycation end products and superoxide dismutase-2 (SOD-2) in ventricular tissues compared to Tat(−) controls. No changes in SOD-1 or α-smooth muscle actin were observed. Despite Tat-mediated changes at the cellular level, no changes in echocardiographic measures were detected. Tat(+) mice had a greater proportion of ventricular mast cells and collagen; however, doxycycline exposure offset the latter effect. These data suggest that Tat exposure promotes cellular changes that can precede progression to CVD.

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The Physiological and Pathological Roles of Mitochondrial Calcium Uptake in Heart

Cited by 19 publications

References 96 publications

The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

Potential cardiotoxicity induced by Euodiae Fructus: In vivo and in vitro experiments and untargeted metabolomics research

HIV-1 Tat Upregulates the Receptor for Advanced Glycation End Products and Superoxide Dismutase-2 in the Heart of Transgenic Mice

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