The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform

Wei-jan Chen - One of the best experts on this subject based on the ideXlab platform.

  • Tachycardia-induced CD44/NOX4 signaling is involved in the development of atrial remodeling.
    Journal of molecular and cellular cardiology, 2019
    Co-Authors: Wei-jan Chen, Gwo-jyh Chang, Ying-ju Lai, Shang-hung Chang, Yi-hsin Chan, Jia-lin Lee, Feng-chun Tsai, Yung-hsin Yeh
    Abstract:

    Atrial fibrillation (AF) is associated with oxidative stress and Ca2+-handling abnormalities in atrial myocytes. Our prior study has demonstrated the involvement of CD44, a membrane receptor for hyaluronan (HA), in the pathogenesis of AF. This study further evaluated whether CD44 and its related signaling mediate atrial tachycardia-induced oxidative stress and Ca2+-handling abnormalities. Tachypacing in atrium-derived myocytes (HL-1 Cell Line) induced the activation of CD44-related signaling, including HA and HA synthase (HAS) expression. Blocking HAS/HA/CD44 signaling attenuated tachypacing-induced oxidative stress (NADPH oxidase [NOX] 2/4 expression) and Ca2+-handling abnormalities (oxidized Ca2+/calmodulin-dependent protein kinase II [ox-CaMKII] and phospho-ryanodine receptor type 2 [p-RyR2] expression) in HL-1 myocytes. Furthermore, a direct association between CD44 and NOX4 was documented in tachy-paced HL-1 myocytes and atrial tissues from AF patients. In vitro, Ca2+ spark frequencies in atrial myocytes isolated from CD44-/- mice were lower than those from wild-type mice. Furthermore, administration of an anti-CD44 blocking antibody in atrial myocytes isolated from wild-type mice diminished the frequency of Ca2+ spark. Ex vivo tachypacing models of CD44-/- mice exhibited a lower degree of oxidative stress and expression of ox-CaMKII/p-RyR2 in their atria than those of wild-type mice. In vivo, burst atrial pacing stimulated a less inducibility of AF in CD44-/-mice than in wild-type mice. In conclusion, atrial tachypacing-induced Ca2+-handling abnormalities are mediated via CD44/NOX4 signaling, which provides a possible explanation for the development of AF.

  • Protective role of heme oxygenase-1 in atrial remodeling
    Basic Research in Cardiology, 2016
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Ying-hwa Chen, Lung-an Hsu, Wei-jan Chen
    Abstract:

    Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 Cell Line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 Cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1^−/− mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1^−/− mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development.

  • Rosuvastatin suppresses atrial tachycardia-induced Cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway.
    Journal of molecular and cellular cardiology, 2015
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Ying-hwa Chen, Ying-ju Lai, Mei-ling Cheng, Wei-jan Chen
    Abstract:

    Atrial fibrillation (AF) is associated with structural remodeling in atrial myocytes. Emerging evidence suggests that statin has a protective effect on AF through cholesterol-independent mechanisms. The aim of this study is to investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system, mediates the suppressive effect of statin on atrial tachycardia-induced structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 Cell Line) with rosuvastatin enhanced HO-1 expression/activity and attenuated tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1 inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO-1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of-function study demonstrated that Akt/Nrf2 pathways lay to the up-stream of HO-1 in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway in the antioxidant effect of rosuvastatin was documented in an ex vivo tachypacing model. The suppressive effect of statin on atrial tachypacing-induced Cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling, which provides a possible explanation for the protective effect of statin on AF.

  • Transforming growth factor-β and oxidative stress mediate tachycardia-induced Cellular remodelling in cultured atrial-derived myocytes
    Cardiovascular research, 2011
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Feng-chun Tsai, Ting-hsiang Chan, Stanley Nattel, Wei-jan Chen
    Abstract:

    Aims Atrial fibrillation (AF), a common tachyarrhythmia in clinical practice, is associated with increased oxidative stress. Structural remodeling in atrial myocytes, including myofibril degradation, is an important characteristic of AF. However, the mechanism underlying AF-induced Cellular structural remodeling remains unclear. The aim of this study was to investigate the role of oxidative stress and related factors in tachycardia-induced atrial structural remodeling Methods and results Cultured atrial-derived myocytes (HL-1 Cell Line) were subjected to electrical stimulation. Immunofluorescence and immunoblotting were used to evaluate oxidative stress, myofibril degradation, and transforming growth factor-β (TGF-β) expression. Tachypacing in HL-1 Cells induced TGF-β expression, pronounced oxidative stress including up-regulation of NADPH oxidases (Nox2/4), and degradation of myofibril. Oxidative stress scavenger, NADPH oxidase inhibitors, and small-interfering RNAs for Nox2/4 blocked tachypacing-induced myofibril degradation, suggesting that Nox-derived oxidative stress may lead to tachycardia-induced myofibril degradation. Blockade of TGF-β signaling by neutralizing TGF-β antibodies attenuated myofibril loss in response to tachypacing, implicating autocrine and/or paracrine roles for TGF-β in such effects. Tachypacing also induced the activation of p-Smad3 (an effective mediator of TGF-β) and small-interfering RNAs for Nox2/4 attenuated its activation, supporting a crosstalk between both signaling pathways. Furthermore, TGF-β expression, oxidative stress, and myofibril loss were greater in the atria of patients with AF than those with sinus rhythm. Conclusions Rapid activation in atrial myocytes promotes myofibril degradation through autocrine/paracrine TGF-β signaling and increased oxidative stress. These findings provide an important mechanistic insight into AF-related structural remodeling.

Yung-hsin Yeh - One of the best experts on this subject based on the ideXlab platform.

  • Tachycardia-induced CD44/NOX4 signaling is involved in the development of atrial remodeling.
    Journal of molecular and cellular cardiology, 2019
    Co-Authors: Wei-jan Chen, Gwo-jyh Chang, Ying-ju Lai, Shang-hung Chang, Yi-hsin Chan, Jia-lin Lee, Feng-chun Tsai, Yung-hsin Yeh
    Abstract:

    Atrial fibrillation (AF) is associated with oxidative stress and Ca2+-handling abnormalities in atrial myocytes. Our prior study has demonstrated the involvement of CD44, a membrane receptor for hyaluronan (HA), in the pathogenesis of AF. This study further evaluated whether CD44 and its related signaling mediate atrial tachycardia-induced oxidative stress and Ca2+-handling abnormalities. Tachypacing in atrium-derived myocytes (HL-1 Cell Line) induced the activation of CD44-related signaling, including HA and HA synthase (HAS) expression. Blocking HAS/HA/CD44 signaling attenuated tachypacing-induced oxidative stress (NADPH oxidase [NOX] 2/4 expression) and Ca2+-handling abnormalities (oxidized Ca2+/calmodulin-dependent protein kinase II [ox-CaMKII] and phospho-ryanodine receptor type 2 [p-RyR2] expression) in HL-1 myocytes. Furthermore, a direct association between CD44 and NOX4 was documented in tachy-paced HL-1 myocytes and atrial tissues from AF patients. In vitro, Ca2+ spark frequencies in atrial myocytes isolated from CD44-/- mice were lower than those from wild-type mice. Furthermore, administration of an anti-CD44 blocking antibody in atrial myocytes isolated from wild-type mice diminished the frequency of Ca2+ spark. Ex vivo tachypacing models of CD44-/- mice exhibited a lower degree of oxidative stress and expression of ox-CaMKII/p-RyR2 in their atria than those of wild-type mice. In vivo, burst atrial pacing stimulated a less inducibility of AF in CD44-/-mice than in wild-type mice. In conclusion, atrial tachypacing-induced Ca2+-handling abnormalities are mediated via CD44/NOX4 signaling, which provides a possible explanation for the development of AF.

  • Protective role of heme oxygenase-1 in atrial remodeling
    Basic Research in Cardiology, 2016
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Ying-hwa Chen, Lung-an Hsu, Wei-jan Chen
    Abstract:

    Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 Cell Line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 Cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1^−/− mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1^−/− mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development.

  • Rosuvastatin suppresses atrial tachycardia-induced Cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway.
    Journal of molecular and cellular cardiology, 2015
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Ying-hwa Chen, Ying-ju Lai, Mei-ling Cheng, Wei-jan Chen
    Abstract:

    Atrial fibrillation (AF) is associated with structural remodeling in atrial myocytes. Emerging evidence suggests that statin has a protective effect on AF through cholesterol-independent mechanisms. The aim of this study is to investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system, mediates the suppressive effect of statin on atrial tachycardia-induced structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 Cell Line) with rosuvastatin enhanced HO-1 expression/activity and attenuated tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1 inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO-1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of-function study demonstrated that Akt/Nrf2 pathways lay to the up-stream of HO-1 in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway in the antioxidant effect of rosuvastatin was documented in an ex vivo tachypacing model. The suppressive effect of statin on atrial tachypacing-induced Cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling, which provides a possible explanation for the protective effect of statin on AF.

  • Transforming growth factor-β and oxidative stress mediate tachycardia-induced Cellular remodelling in cultured atrial-derived myocytes
    Cardiovascular research, 2011
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Feng-chun Tsai, Ting-hsiang Chan, Stanley Nattel, Wei-jan Chen
    Abstract:

    Aims Atrial fibrillation (AF), a common tachyarrhythmia in clinical practice, is associated with increased oxidative stress. Structural remodeling in atrial myocytes, including myofibril degradation, is an important characteristic of AF. However, the mechanism underlying AF-induced Cellular structural remodeling remains unclear. The aim of this study was to investigate the role of oxidative stress and related factors in tachycardia-induced atrial structural remodeling Methods and results Cultured atrial-derived myocytes (HL-1 Cell Line) were subjected to electrical stimulation. Immunofluorescence and immunoblotting were used to evaluate oxidative stress, myofibril degradation, and transforming growth factor-β (TGF-β) expression. Tachypacing in HL-1 Cells induced TGF-β expression, pronounced oxidative stress including up-regulation of NADPH oxidases (Nox2/4), and degradation of myofibril. Oxidative stress scavenger, NADPH oxidase inhibitors, and small-interfering RNAs for Nox2/4 blocked tachypacing-induced myofibril degradation, suggesting that Nox-derived oxidative stress may lead to tachycardia-induced myofibril degradation. Blockade of TGF-β signaling by neutralizing TGF-β antibodies attenuated myofibril loss in response to tachypacing, implicating autocrine and/or paracrine roles for TGF-β in such effects. Tachypacing also induced the activation of p-Smad3 (an effective mediator of TGF-β) and small-interfering RNAs for Nox2/4 attenuated its activation, supporting a crosstalk between both signaling pathways. Furthermore, TGF-β expression, oxidative stress, and myofibril loss were greater in the atria of patients with AF than those with sinus rhythm. Conclusions Rapid activation in atrial myocytes promotes myofibril degradation through autocrine/paracrine TGF-β signaling and increased oxidative stress. These findings provide an important mechanistic insight into AF-related structural remodeling.

Gwo-jyh Chang - One of the best experts on this subject based on the ideXlab platform.

  • Tachycardia-induced CD44/NOX4 signaling is involved in the development of atrial remodeling.
    Journal of molecular and cellular cardiology, 2019
    Co-Authors: Wei-jan Chen, Gwo-jyh Chang, Ying-ju Lai, Shang-hung Chang, Yi-hsin Chan, Jia-lin Lee, Feng-chun Tsai, Yung-hsin Yeh
    Abstract:

    Atrial fibrillation (AF) is associated with oxidative stress and Ca2+-handling abnormalities in atrial myocytes. Our prior study has demonstrated the involvement of CD44, a membrane receptor for hyaluronan (HA), in the pathogenesis of AF. This study further evaluated whether CD44 and its related signaling mediate atrial tachycardia-induced oxidative stress and Ca2+-handling abnormalities. Tachypacing in atrium-derived myocytes (HL-1 Cell Line) induced the activation of CD44-related signaling, including HA and HA synthase (HAS) expression. Blocking HAS/HA/CD44 signaling attenuated tachypacing-induced oxidative stress (NADPH oxidase [NOX] 2/4 expression) and Ca2+-handling abnormalities (oxidized Ca2+/calmodulin-dependent protein kinase II [ox-CaMKII] and phospho-ryanodine receptor type 2 [p-RyR2] expression) in HL-1 myocytes. Furthermore, a direct association between CD44 and NOX4 was documented in tachy-paced HL-1 myocytes and atrial tissues from AF patients. In vitro, Ca2+ spark frequencies in atrial myocytes isolated from CD44-/- mice were lower than those from wild-type mice. Furthermore, administration of an anti-CD44 blocking antibody in atrial myocytes isolated from wild-type mice diminished the frequency of Ca2+ spark. Ex vivo tachypacing models of CD44-/- mice exhibited a lower degree of oxidative stress and expression of ox-CaMKII/p-RyR2 in their atria than those of wild-type mice. In vivo, burst atrial pacing stimulated a less inducibility of AF in CD44-/-mice than in wild-type mice. In conclusion, atrial tachypacing-induced Ca2+-handling abnormalities are mediated via CD44/NOX4 signaling, which provides a possible explanation for the development of AF.

  • Protective role of heme oxygenase-1 in atrial remodeling
    Basic Research in Cardiology, 2016
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Ying-hwa Chen, Lung-an Hsu, Wei-jan Chen
    Abstract:

    Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 Cell Line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 Cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1^−/− mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1^−/− mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development.

  • Rosuvastatin suppresses atrial tachycardia-induced Cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway.
    Journal of molecular and cellular cardiology, 2015
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Ying-hwa Chen, Ying-ju Lai, Mei-ling Cheng, Wei-jan Chen
    Abstract:

    Atrial fibrillation (AF) is associated with structural remodeling in atrial myocytes. Emerging evidence suggests that statin has a protective effect on AF through cholesterol-independent mechanisms. The aim of this study is to investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system, mediates the suppressive effect of statin on atrial tachycardia-induced structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 Cell Line) with rosuvastatin enhanced HO-1 expression/activity and attenuated tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1 inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO-1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of-function study demonstrated that Akt/Nrf2 pathways lay to the up-stream of HO-1 in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway in the antioxidant effect of rosuvastatin was documented in an ex vivo tachypacing model. The suppressive effect of statin on atrial tachypacing-induced Cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling, which provides a possible explanation for the protective effect of statin on AF.

  • Transforming growth factor-β and oxidative stress mediate tachycardia-induced Cellular remodelling in cultured atrial-derived myocytes
    Cardiovascular research, 2011
    Co-Authors: Yung-hsin Yeh, Chi-tai Kuo, Gwo-jyh Chang, Feng-chun Tsai, Ting-hsiang Chan, Stanley Nattel, Wei-jan Chen
    Abstract:

    Aims Atrial fibrillation (AF), a common tachyarrhythmia in clinical practice, is associated with increased oxidative stress. Structural remodeling in atrial myocytes, including myofibril degradation, is an important characteristic of AF. However, the mechanism underlying AF-induced Cellular structural remodeling remains unclear. The aim of this study was to investigate the role of oxidative stress and related factors in tachycardia-induced atrial structural remodeling Methods and results Cultured atrial-derived myocytes (HL-1 Cell Line) were subjected to electrical stimulation. Immunofluorescence and immunoblotting were used to evaluate oxidative stress, myofibril degradation, and transforming growth factor-β (TGF-β) expression. Tachypacing in HL-1 Cells induced TGF-β expression, pronounced oxidative stress including up-regulation of NADPH oxidases (Nox2/4), and degradation of myofibril. Oxidative stress scavenger, NADPH oxidase inhibitors, and small-interfering RNAs for Nox2/4 blocked tachypacing-induced myofibril degradation, suggesting that Nox-derived oxidative stress may lead to tachycardia-induced myofibril degradation. Blockade of TGF-β signaling by neutralizing TGF-β antibodies attenuated myofibril loss in response to tachypacing, implicating autocrine and/or paracrine roles for TGF-β in such effects. Tachypacing also induced the activation of p-Smad3 (an effective mediator of TGF-β) and small-interfering RNAs for Nox2/4 attenuated its activation, supporting a crosstalk between both signaling pathways. Furthermore, TGF-β expression, oxidative stress, and myofibril loss were greater in the atria of patients with AF than those with sinus rhythm. Conclusions Rapid activation in atrial myocytes promotes myofibril degradation through autocrine/paracrine TGF-β signaling and increased oxidative stress. These findings provide an important mechanistic insight into AF-related structural remodeling.

Robert S. Adelstein - One of the best experts on this subject based on the ideXlab platform.

  • ablation of nonmuscle myosin ii b and ii c reveals a role for nonmuscle myosin ii in cardiac myocyte karyokinesis
    Molecular Biology of the Cell, 2010
    Co-Authors: Siddhartha S. Jana, Mary Anne Conti, William C Claycomb, Sachiyo Kawamoto, Robert S. Adelstein
    Abstract:

    Ablation of nonmuscle myosin (NM) II-A or NM II-B results in mouse embryonic lethality. Here, we report the results of ablating NM II-C as well as NM II-C/II-B together in mice. NM II-C ablated mice survive to adulthood and show no obvious defects compared with wild-type littermates. However, ablation of NM II-C in mice expressing only 12% of wild-type amounts of NM II-B results in a marked increase in cardiac myocyte hypertrophy compared with the NM II-B hypomorphic mice alone. In addition, these hearts develop interstitial fibrosis associated with diffuse N-cadherin and β-catenin localization at the intercalated discs, where both NM II-B and II-C are normally concentrated. When both NM II-C and II-B are ablated the B−C−/B−C− cardiac myocytes show major defects in karyokinesis. More than 90% of B−C−/B−C− myocytes demonstrate defects in chromatid segregation and mitotic spindle formation accompanied by increased stability of microtubules and abnormal formation of multiple centrosomes. This requirement for NM II in karyokinesis is further demonstrated in the HL-1 Cell Line derived from mouse atrial myocytes, by using small interfering RNA knockdown of NM II or treatment with the myosin inhibitor blebbistatin. Our study shows that NM II is involved in regulating cardiac myocyte karyokinesis by affecting microtubule dynamics.

Andrea A. Robitzki - One of the best experts on this subject based on the ideXlab platform.

  • DIGE Proteome Analysis Reveals Suitability of Ischemic Cardiac In Vitro Model for Studying Cellular Response to Acute Ischemia and Regeneration
    PloS one, 2012
    Co-Authors: Sina Haas, Heinz-georg Jahnke, Nora Moerbt, Martin Von Bergen, Seyedhossein Aharinejad, O. Andrukhova, Andrea A. Robitzki
    Abstract:

    Proteomic analysis of myocardial tissue from patient population is suited to yield insights into Cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 Cell Line. To identify pathways involved in the Cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, Cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy. With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research.

  • A microelectrode-based sensor for label-free in vitro detection of ischemic effects on cardiomyocytes.
    Biosensors & bioelectronics, 2009
    Co-Authors: Dana Krinke, Heinz-georg Jahnke, Oliver Pänke, Andrea A. Robitzki
    Abstract:

    Heart diseases represent the most common cause of death in industrialised countries. For this reason target identification and development of novel anti-target drugs are in the focus of pharmaceutical industry. Especially cardiac infarct is a topical field of research. A bottleneck in today's long-duration and high-cost drug development is the lack of fast, label-free and Cell-based high throughput/high content screening (HTS/HCS) assays for bridging the gap between Cell-free screening and animal experiments. Here, we report for the first time on an in vitro cardiac ischemic model, where pathological consequences of simulated cardiac infarct can be detected quantitatively by microelectrode array-based impedance spectroscopy. Using the contractile HL-1 Cell Line and defined ischemic conditions we were able to develop a standardised and reproducible pathologic model. We characterised and verified the HL-1 based ischemic model by apoptosis and proliferation assays as well as immunochemical analysis of Cell-Cell junctions. We showed that the observed Cell and biomolecular effects correspond with results obtained by impedance spectroscopy. Functionality of the impedimetric assay was demonstrated by real-time detection of reduced pathological effects due to application of the selective Rac1 inhibitor NCS23766. Numerical analysis by means of an equivalent circuit allowed the quantification of changes in resistance and capacitance of the adherent Cell layer after ischemic treatment and application of NSC23766 as drug model. Our findings provide a novel Cell-based real-time screening system for testing drug candidates against cardiac infarct and its implications.