Sodium calcium exchanger plays a key role in alteration of cardiac function in response to pressure overload

Takimoto, Eiki; Yao, Atsushi; Toko, Haruhiro; Takano, Hiroyuki; Shimoyama, Masaki; Sonoda, Makoto; Wakimoto, Koji; Takahashi, Toshiyuki; Akazawa, Hiroshi; Mizukami, Masaaki; Nagai, Toshio; Nagai, Ryozo; Komuro, Issei

doi:10.1096/fj.01-0735com

Cited by 28 publications

(22 citation statements)

References 44 publications

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“…For example, it relates to contractile dysfunction, arrhythmogenesis and remodeling of cardiac muscles [33, 34, 35], to abnormal Ca 2+ regulation in pancreatic cells [36, 37], and to the abnormal development of brain cells [38, 39]. In cultured human and rat MCs, the expression of NCX was shown to be related to the rate of growth and life span [40, 41, 42].…”

Section: Discussionmentioning

confidence: 99%

Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell

et al. 2003

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Background: A number of cellular mechanisms are critically dependent on intracellular Ca²⁺ homeostasis. A sustained increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) is capable of activating a number of potentially harmful processes including phenotype change to secretory type, dysregulated cell proliferation, and cell injury and death. Mesangial cells (MCs) play an important role in the pathophysiology of diabetic nephropathy. Methods: We evaluated the effect of high glucose on basal [Ca²⁺]_i in the unstimulated state and identified its contributing pathways. MCs were isolated and cultured from Sprague-Dawley rats. [Ca²⁺]_i was measured by fluorometric technique with fura-2AM. Results: In a dose-dependent manner, superfusion of MCs with Tyrode’s solution containing high glucose (30 and 50 mM) induced a delayed spontaneous increase in [Ca²⁺]_i, which was not found in those with normal (5.5 mM) glucose or mannitol. The high glucose-induced increase in [Ca²⁺]_ioccurred through transmembrane influx of extracellular Ca²⁺ and was blocked by SKF96365, an inhibitor of store-operated Ca²⁺ influx. Na⁺-Ca²⁺ exchanger (NCX) activity, a major channel regulating basal [Ca²⁺]_i, and the clearing ability of intracellular Ca²⁺ were depressed after MCs were cultured in high-glucose medium. Western blot analysis revealed the decreased expression of a 70-kD NCX protein in MCs cultured in high-glucose medium. Conclusions: A high-glucose concentration induced a spontaneous increase in basal [Ca²⁺]_i of MCs without stimulation. There was a decrease in the activity of NCX in the high-glucose condition, which seems to occur at the level of protein expression. The present results provide a novel insight into the mechanisms of diabetic nephropathy in that intracellular Ca²⁺ homeostasis is an important secondary messenger and a mediator in hormonal signaling.

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Section: Discussionmentioning

confidence: 99%

Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell

et al. 2003

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“…MAO-B -/ -mice were generated as previously described (20). TAC was performed following a previously reported protocol (40). After induction of anesthesia and intubation, mice were placed on a volume ventilator (120 breaths/min, 1.2 ml/g/min) and anesthesia was maintained with 5% isofluorane.…”

Section: Mao-bmentioning

confidence: 99%

Monoamine Oxidase B Prompts Mitochondrial and Cardiac Dysfunction in Pressure Overloaded Hearts

Kaludercic

Carpi

Nagayama

et al. 2014

Antioxidants & Redox Signaling

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138

132

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Aims: Monoamine oxidases (MAOs) are mitochondrial flavoenzymes responsible for neurotransmitter and biogenic amines catabolism. MAO-A contributes to heart failure progression via enhanced norepinephrine catabolism and oxidative stress. The potential pathogenetic role of the isoenzyme MAO-B in cardiac diseases is currently unknown. Moreover, it is has not been determined yet whether MAO activation can directly affect mitochondrial function. Results: In wild type mice, pressure overload induced by transverse aortic constriction (TAC) resulted in enhanced dopamine catabolism, left ventricular (LV) remodeling, and dysfunction. Conversely, mice lacking MAO-B (MAO-B -/ -) subjected to TAC maintained concentric hypertrophy accompanied by extracellular signal regulated kinase (ERK)1/2 activation, and preserved LV function, both at early (3 weeks) and late stages (9 weeks). Enhanced MAO activation triggered oxidative stress, and dropped mitochondrial membrane potential in the presence of ATP synthase inhibitor oligomycin both in neonatal and adult cardiomyocytes. The MAO-B inhibitor pargyline completely offset this change, suggesting that MAO activation induces a latent mitochondrial dysfunction, causing these organelles to hydrolyze ATP. Moreover, MAO-dependent aldehyde formation due to inhibition of aldehyde dehydrogenase 2 activity also contributed to alter mitochondrial bioenergetics. Innovation: Our study unravels a novel role for MAO-B in the pathogenesis of heart failure, showing that both MAO-driven reactive oxygen species production and impaired aldehyde metabolism affect mitochondrial function. Conclusion: Under conditions of chronic hemodynamic stress, enhanced MAO-B activity is a major determinant of cardiac structural and functional disarrangement. Both increased oxidative stress and the accumulation of aldehyde intermediates are likely liable for these adverse morphological and mechanical changes by directly targeting mitochondria. Antioxid. Redox Signal. 20, 267-280.

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“…96 Further experiments are necessary to rule out the possibility that NCX knockout mice develop adaptive compensatory mechanisms responsible for the hypertrophic response.…”

Section: Models Of Cardiac Hypertrophy In Which Nhe-1 Plays a Rolementioning

confidence: 99%

Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy

2007

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Sodium calcium exchanger plays a key role in alteration of cardiac function in response to pressure overload

Cited by 28 publications

References 44 publications

Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell

Effect of High Glucose on Basal Intracellular Calcium Regulation in Rat Mesangial Cell

Monoamine Oxidase B Prompts Mitochondrial and Cardiac Dysfunction in Pressure Overloaded Hearts

Sodium-Hydrogen Exchanger, Cardiac Overload, and Myocardial Hypertrophy

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