Increased Reactive Oxygen Species and Anti-Oxidative Response in Mitochondrial Cardiomyopathy

Ishikawa, Kazunobu; Kimura, Satoshi; Kobayashi, Atsushi; Sato, Toshio; Matsumoto, Hayato; Ujiie, Yuichi; Nakazato, Kazuhiko; Mitsugi, Minoru; Maruyama, Yukio

doi:10.1253/circj.69.617

Cited by 23 publications

(16 citation statements)

References 9 publications

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“…These data suggested that the A3243G mutation in the heteroplasmic tissues caused a subtle defect in respiratory chain function, and the severity of mitochondrial respiratory deficiency in the brains was higher possibly owning to the higher proportion of mutant mtDNA. The finding of impaired respiratory function in the chimeric mice is in agreement with previous reports that the primary consequence of this mutation is a reduction in combined complex I/IV activities (Ishikawa et al, 2005;McKenzie et al, 2004McKenzie et al, , 2007 Table 1. Activities of mitochondrial complex I-IV in the heteroplasmic tissues of chimera mice.…”

Section: Chimera Mice Carrying A3243g Mutation Exhibited Low Mitochonsupporting

confidence: 92%

“…Besides the energy defect, A3243G mutation also causes ROS associated diseases' pathophysiology (Ishikawa et al, 2005;Vergani et al, 2007). For example, the A3243G mutation has been shown to increase total SOD and catalase activities in myoblasts (Rusanen et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence from patients and in vitro studies suggests that mitochondrial dysfunction, either a primary (e.g., respiratory chain abnormalities) or a secondary (elevated ROS and control of apoptosis) event, plays an important role in the pathogenesis of mtDNA-based diseases (Ishikawa et al, 2005;Vives-Bauza et al, 2006;McKenzie et al, 2004McKenzie et al, , 2007. Patients carrying A3243G mutation exhibited an impaired oxidative phosphorylation with a deficient activity of respiratory chain complexes, increased ROS production, and significant induction of heme oxygenase-1 (Ishikawa et al, 2005). In vitro studies revealed the A3243G mutation impaired RNA processing, aminoacylation, post-transcriptional tRNA modification, and translation (Mkaouar-Rebai et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation

Li¹,

Zhou²,

Meng³

et al. 2008

Genet. Mol. Res.

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ABSTRACT. The mitochondrial A3243G tRNALeu(UUR) mutation associated with a variety of mitochondrial disorders results in a severe respiratory deficiency, an increase in reactive oxygen species (ROS) production and activities of anti-oxidative enzyme in vitro. However, the phenotypic implications of this mutation have not been described in vivo. Here, mitochondria carrying A3243G transition from the peripheral blood of diabetes mellitus patients were microinjected into zygotes. Influence of this mutation on mitochondrial respiratory enzyme activities, ROS generation, and antioxidative enzyme activities in the heteroplasmic tissues of transmitochondrial mice was evaluated. The chimeric mice exhibited a subtle impaired oxidative phosphorylation, reduced activity of complex I/IV, increased activity of superoxide dismutase, and in turn, enhanced ROS generation. Our results suggest that mitochondrial 1055 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 7 (4): 1054-1062 (2008) ROS generation and SOD activity in transmitochondrial mice A3243G mutation may be responsible for the high ROS production in vivo. Increased generation of ROS caused by mtDNA mutation may also play a role in the pathogenesis of the A3243G mutationassociated diseases.

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Section: Chimera Mice Carrying A3243g Mutation Exhibited Low Mitochonsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation

Li¹,

Zhou²,

Meng³

et al. 2008

Genet. Mol. Res.

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“…9 Remondino et al reported that BAR activation rapidly provoked oxidative stress via the phosphorylation of JNK and p38 MAP kinases. 8 The ROS production in the mitochondria contributes to pathological process such as cardiomyopathy, 32 aging, 33 apoptosis, 34 hypoxia, 35 and ischemia/reperfusion. 36,37 The complexes I and III of the mitochondrial electron transport chain (ETC) are regarded as the major sites of ROS production.…”

Section: Pkacat-induced Ros Generation In Mitochondriamentioning

confidence: 99%

Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species

Nagasaka

Katoh

Niu

et al. 2007

Circ J

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“…[2][3][4] Betaadrenergic receptor blockers have been shown to be effective for interrupting this malignant cycle of heart failure, thus attenuating both the calcium overload and the mitochondrial dysfunction. 5,6 However, a recent clinical study, COMET, suggested that carvedilol had a better effect on the survival rate in patients with chronic heart failure than metoprolol.…”

mentioning

confidence: 99%

Carvedilol Inhibits Mitochondrial Oxygen Consumption and Superoxide Production During Calcium Overload in Isolated Heart Mitochondria

Kametani

Miura

Harada

et al. 2006

Circ J

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n the failing myocardium, calcium overload has been shown to play an important role in causing a dysfunction in the myocardium, 1 and the reactive oxygen species (ROS) are produced from impaired mitochondria, which thus further impairs the cellular function. [2][3][4] Betaadrenergic receptor blockers have been shown to be effective for interrupting this malignant cycle of heart failure, thus attenuating both the calcium overload and the mitochondrial dysfunction. 5,6 However, a recent clinical study, COMET, suggested that carvedilol had a better effect on the survival rate in patients with chronic heart failure than metoprolol. 7 This study proposed that 2-adrenergic blocking, -adrenergic receptor blocking, and other antioxidant effects might play a role in this occurrence. However, the underlying mechanism has yet to be well clarified. We hypothesized that carvedilol directly modifies the mitochondrial function, whereas also inhibiting the mitochondrial ROS production, especially from complex I 8 by -, -adrenergic receptor-independent mechanisms. To test this hypothesis, we isolated the rat heart mitochondria and evaluated the direct effect of carvedilol and metoprolol on the mitochondrial function, regarding such factors as the oxygen consumption and ROS production during calcium overload. Circulation Journal Vol.70, March 2006 Methods AnimalsMale Sprague -Dawley rats (7-9 weeks old, 300-350 g) were anesthetized with the intra-peritoneal injection of sodium pentobarbital (60 mg/kg) and then the heart was excised and rinsed with an ice-cold buffer containing 300 mmol/L mannitol, 10 mmol/L HEPES, 0.2 mmol/L EDTA, and 0.1% bovine serum albumin (BSA). The pH was adjusted to 7.4 with KOH. The hearts were trimmed and homogenized with a motor-driven Teflon Potter homogenizer for 1 min in an ice-cold buffer. Isolation of Heart MitochondriaMitochondria were then isolated by the centrifuge method, as previously described with slight modifications. 9,10 The heart homogenate was centrifuged at 700 G for 10 min at 4°C using the KUBOTA 3780 centrifuge. The supernatant was decanted and centrifuged at 5,000 G for 8 min, followed by 10,000 G for 5 min. The pellet was resuspended using a paint brush and then it was centrifuged at 2,500 G for 10 min, followed by 9,000 G for 10 min. EDTA was omitted from the final washing buffer. The mitochondrial protein concentration was determined by the Bradford method using BSA as a standard. The mitochondrial suspension (4 mg/ml) was kept on ice until the measurements were performed, which were carried out after a 20-min recovery. All experiments conformed to the Guide for the Care and Use of Laboratory Animals Background The COMET study suggested the better effect of carvedilol to metoprolol in treating heart failure. However, its underlying mechanisms of action remain unclear. As a result, evaluation of the distinct effects of both drugs on the mitochondrial function and reactive oxygen species (ROS) production during Ca 2+ overload was investigated. Methods and ResultsThe mitochondrial...

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Increased Reactive Oxygen Species and Anti-Oxidative Response in Mitochondrial Cardiomyopathy

Cited by 23 publications

References 9 publications

Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation

Increased ROS generation and SOD activity in heteroplasmic tissues of transmitochondrial mice with A3243G mitochondrial DNA mutation

Protein Kinase A Catalytic Subunit Alters Cardiac Mitochondrial Redox State and Membrane Potential Via the Formation of Reactive Oxygen Species

Carvedilol Inhibits Mitochondrial Oxygen Consumption and Superoxide Production During Calcium Overload in Isolated Heart Mitochondria

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