Decreasing expression of α1C calcium L-type channel subunit mRNA in rat ventricular myocytes upon manganese exposure

Yang, Huijuan; Wang, Tian-Nan; Li, Jieyue; Gu, Ling; Zheng, Xiaoxiang

doi:10.1002/jbt.20133

Cited by 10 publications

(17 citation statements)

References 30 publications

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“…On the other hand, other results point to the toxic action of high levels of manganese which are manifested in sinus tachycardia, brachycardia, arrhythmia, sinister megacardia, and accelerated heart-beat (11). These outcomes are associated with manganese interaction with the L-type calcium channel in the cardiovascular system (34). Our ECG results show that shortterm, high-dose treatment with MnCl 2 did not cause any serious disturbances except for slightly shortened QT and RR intervals.…”

Section: Discussionmentioning

confidence: 63%

Cambios en el ECG y la actividad enzimática en corazón de rata tras infarto de miocardio: efecto de la TPP y del MnCl2

Tylicki

Czerniecki

Godlewska

et al. 2008

J. Physiol. Biochem.

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Heart infarction is one of the main causes of death in the human population. Assurance of a sufficient level of bioenergetic processes is very important for the heart after infarction. Mn2+ as well as thiamine pyrophosphate (TPP) are positive effectors of the pyruvate dehydrogenase complex (PDH) and the 2-oxoglutarate dehydrogenase complex (OGDH), both of which play a very important role in the Krebs cycle. Thus, we have established the effect of MnCl2 (10mg/kg) and TPP (20mg/kg)--4 injections every 12 h--on the activity of PDH, OGDH, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH). Additionally, we perform an analysis of ECG to affirm the changes in the heart electrophysiology of healthy rats after MnCl2 and TPP treatment. We then analyzed changes in the activity of these enzymes after experimental myocardial infarction in rats. We observed a decrease of OGDH and MDH activity in rat hearts after infarction in comparison with sham-operated rats. Treatment of healthy rats with MnCl2 caused an increase of OGDH activity. Moreover both MnCl2 and TPP caused an increase of PDH activity and a decrease of MDH activity (TPP revealed a stronger effect). We found no changes in LDH activity. Electrocardiography data showed a slight shortening of the QT interval and an enhanced heartbeat rate after treatment with MnCl2. TPP caused only elongation of the QT interval. In conclusion, application of MnCl2 enhanced the activity of some very important enzymes in the respiration process (PDH and OGDH). This effect, connected with enhanced heartbeat and a slightly shortened ventricle relaxation, may have potential application during the key period of convalescence following heart infarction.

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Section: Discussionmentioning

confidence: 63%

Cambios en el ECG y la actividad enzimática en corazón de rata tras infarto de miocardio: efecto de la TPP y del MnCl2

Tylicki

Czerniecki

Godlewska

et al. 2008

J. Physiol. Biochem.

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“…The animal study's ethics and animal care was approved by the institution. Single rat ventricular myocytes were obtained by an enzymatic dissociation technique (Yang et al 2006). The Sprague-Dawley rat (either sex, weighing 150-180g) was sacrificed, and the heart was quickly excised and placed in oxygenated cold (4 • C) Ca 2+ -free MOPS solution.…”

Section: Preparation Of Ventricular Myocytesmentioning

confidence: 99%

“…In manganese exposed workers, disturbed autonomic nervous function and changing of cardiac rhythm as well as blood pressure have been observed (Barrington et al 1998). The in vitro studies showed that manganese could block the L-type calcium channel and reduce the heart rate; at the same time the heart retained a high content of manganese and calcium (Brurok et al 1997a;1997b;Yang et al 2006). Manganese is also capable of restraining the function of proton pump and reducing mitochondrial membrane potential, resulting in injury to myocardial cells (Jiang and Zheng 2005).…”

Section: Introductionmentioning

confidence: 95%

“…Owing to the close relationship, the monitoring of variation of GSH level and ROS level in the response to external stimuli are very important. But few were done to investigate the ROS generation and the level of GSH under manganese toxicity in myocytes, although its damage to the heart was obvious, even inducing the apoptosis of myocytes (Brurok et al 1997b;Barrington et al 1998;Jiang and Zheng 2005;Yang et al 2006). The purpose of this study was to identify the oxidative stress induced by manganese treatment and its relation to the intracellular GSH content under manganese exposure.…”

Section: Introductionmentioning

confidence: 97%

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Involvement of Hydrogen Peroxide in the Manganese-Induced Myocytes Mitochondrial Membrane Potential Loss

Yang

Zhang

et al. 2008

Toxicology Mechanisms and Methods

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Isolated rat ventricular myocytes were incubated in different manganese concentrations and after that the reactive oxygen species (ROS) generation, the level of reduced glutathione (GSH), and the changes of mitochondrial membrane potential (Deltapsi m) were investigated by a flow cytometer (FACScan) as well as laser scanning confocal microscopy (LSCM). Results showed that, although the total ROS in the cell were increased after manganese treatment, hydrogen peroxide (H(2)O(2)) was the main elevated species while superoxide anion (O(2).(-)) was nearly unchanged. The generation of H(2)O(2) became obvious when the myocytes were incubated in the higher concentration of manganese. The content of GSH in myocytes also decreased after manganese exposure. When the myocytes were incubated with both manganese and GSH-ethylester (GSH-EE), which is permeable to the cell membrane, the generation of H(2)O(2) decreased greatly. The loss of the mitochondrial membrane potential (Deltapsi m) was also induced by manganese incubation. However, with the existence of extracellular GSH-EE the Deltapsi m were rescued. The results suggested that manganese action may lead to the ROS stress upon myocytes which most probably rise from high generation of intracellular H(2)O(2). GSH-EE could effectively clean the over-production of H(2)O(2), indicating that the low level of intracellular GSH was another main reason to the high accumulation of H(2)O(2). The mitochondrial membrane potential was also affected by manganese and rescued by GSH-EE, suggesting that H(2)O(2) was also involved in the manganese damages to the mitochondrial membrane potential.

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“…Manganese could affect neuromuscular transmission by interaction with the mitochondrial calcium uniporter and disturbing the ion balance in muscle membranes [11]. In vitro studies also showed that manganese could block the L-type calcium channels in the heart and reduce the heart rate, in addition to inducing an imbalance of the ions, with retention of high contents of manganese and calcium [12][13][14][15]. Manganese was also capable of restraining the function of the proton pump and reducing the mitochondrial membrane potential, resulting in injury to myocardial cells [7].…”

Section: Introductionmentioning

confidence: 99%

Manganese‐induced apoptosis in rat myocytes

Yang

Sun

Zheng

2007

J Biochem & Molecular Tox

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Manganese can be toxic to the heart, causing dysfunction following long exposure. In our experiments, we examined the cytotoxicity of manganese in neonatal rat ventricular myocytes (NRVM) by MTT assays in vitro. Results showed that after incubation in the different concentrations of manganese for 24 h, apparent cytotoxicity was observed. At 500, 1000, and 1500 2 microM of manganese, the percentage of cell viability dropped to 82% +/- 6.13, 78% +/- 5.28, and 66% +/- 4.22, respectively. When cells were treated for 48 h, all concentrations tested exerted toxic effect; especially from 500 to 1500 microM the cell viability dropped from 67% +/- 4.84 to 37% +/- 3.25. Apoptosis in NRVM was then examined by flow cytometry. Results showed that the percentage of apoptotic cells treated with 500 microM of manganese for 24 h increased from 4% +/- 0.84 to 7% +/- 1.16. After 48 h of incubation, this percentage increased to 11% +/- 0.91. There was no significant difference between control groups (0 microM manganese) after 24 and 48 h incubation. The morphological changes of NRVM nuclei were visualized with the fluorescent DNA-binding dye Hoechst33342 after incubation in 500 microM of manganese for 48 h. Compared with normal nuclei, apoptotic nuclei showed the typical features of fragmentation and condensation. To investigate whether there are any apoptotic gene expression changes during apoptosis, we examined the expression level of Bcl-2, Bax, and P53 mRNAs after treatment with 500 microM of manganese for 48 h. The Bcl-2 mRNA expression decreased while the expression of Bax as well as P53 mRNAs increased. These results suggested that manganese cytotoxicity on NRVM could induce apoptosis in NRVM cells. The apoptosis process might involve, and be promoted by, the changes of the expression levels of P53, Bcl-2, and Bax proteins.

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Decreasing expression of α1C calcium L-type channel subunit mRNA in rat ventricular myocytes upon manganese exposure

Cited by 10 publications

References 30 publications

Cambios en el ECG y la actividad enzimática en corazón de rata tras infarto de miocardio: efecto de la TPP y del MnCl2

Cambios en el ECG y la actividad enzimática en corazón de rata tras infarto de miocardio: efecto de la TPP y del MnCl2

Involvement of Hydrogen Peroxide in the Manganese-Induced Myocytes Mitochondrial Membrane Potential Loss

Manganese‐induced apoptosis in rat myocytes

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