The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Richard W Tsika - One of the best experts on this subject based on the ideXlab platform.
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genetic loss of calcineurin blocks Mechanical Overload induced skeletal muscle fiber type switching but not hypertrophy
Journal of Biological Chemistry, 2004Co-Authors: Stephanie A Parsons, Douglas P Millay, Benjamin J Wilkins, Orlando F Bueno, Gretchen L Tsika, Joel R Neilson, Christine M Liberatore, Katherine E Yutzey, Gerald R Crabtree, Richard W TsikaAbstract:Abstract The serine/threonine phosphatase calcineurin is an important regulator of calcium-activated intracellular responses in eukaryotic cells. In higher eukaryotes, calcium/calmodulin-mediated activation of calcineurin facilitates direct dephosphorylation and nuclear translocation of the transcription factor nuclear factor of activated T-cells (NFAT). Recently, controversy has surrounded the role of calcineurin in mediating skeletal muscle cell hypertrophy. Here we examined the ability of calcineurin-deficient mice to undergo skeletal muscle hypertrophic growth following Mechanical Overload (MOV) stimulation or insulin-like growth factor-1 (IGF-1) stimulation. Two distinct models of calcineurin deficiency were employed: calcineurin Aβ gene-targeted mice, which show a ≈50% reduction in total calcineurin, and calcineurin B1-LoxP-targeted mice crossed with a myosin light chain 1f cre knock-in allele, which show a greater than 80% loss of total calcineurin only in skeletal muscle. Calcineurin Aβ-/- and calcineurin B1-LoxP(fl/fl)-MLC-cre mice show essentially no defects in muscle growth in response to IGF-1 treatment or MOV stimulation, although calcineurin Aβ-/- mice show a basal defect in total fiber number in the plantaris and a mild secondary reduction in growth, consistent with a developmental defect in myogenesis. Both groups of gene-targeted mice show normal increases in Akt activation following MOV or IGF-1 stimulation. However, Overload-mediated fiber-type switching was dramatically impaired in calcineurin B1-LoxP(fl/fl)-MLC-cre mice. NFAT-luciferase reporter transgenic mice failed to show a correlation between IGF-1- or MOV-induced hypertrophy and calcineurin-NFAT-dependent signaling in vivo. We conclude that calcineurin expression is important during myogenesis and fiber-type switching, but not for muscle growth in response to hypertrophic stimuli.
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Multiprotein Complex Formation at the β Myosin Heavy Chain Distal Muscle CAT Element Correlates with Slow Muscle Expression but Not Mechanical Overload Responsiveness
The Journal of biological chemistry, 2001Co-Authors: Dharmesh R. Vyas, John J Mccarthy, Gretchen L Tsika, Richard W TsikaAbstract:Abstract To examine the role of the β-myosin heavy chain (βMyHC) distal muscle CAT (MCAT) element in muscle fiber type-specific expression and Mechanical Overload (MOV) responsiveness, we conducted transgenic and in vitro experiments. In adult transgenic mice, mutation of the distal MCAT element led to significant reductions in chloramphenicol acetyltransferase (CAT) specific activity measured in control soleus and plantaris muscles when compared with wild type transgene β293WT but did not abolish MOV-induced CAT specific activity. Electrophoretic mobility shift assay revealed the formation of a specific low migrating nuclear protein complex (LMC) at the βMyHC MCAT element that was highly enriched only when using either MOV plantaris or control soleus nuclear extract. Scanning mutagenesis of the βMyHC distal MCAT element revealed that only the nucleotides comprising the core MCAT element were essential for LMC formation. The proteins within the LMC when using either MOV plantaris or control soleus nuclear extracts were antigenically related to nominal transcription enhancer factor 1 (NTEF-1), poly(ADP-ribose) polymerase (PARP), and Max. Only in vitro translated TEF-1 protein bound to the distal MCAT element, suggesting that this multiprotein complex is tethered to the DNA via TEF-1. Protein-protein interaction assays revealed interactions between nominal TEF-1, PARP, and Max. Our studies show that for transgene β293 the distal MCAT element is not required for MOV responsiveness but suggest that a multiprotein complex likely comprised of nominal TEF-1, PARP, and Max forms at this element to contribute to basal slow fiber expression.
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Muscle-specific and inducible expression of 293-base pair beta-myosin heavy chain promoter in transgenic mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, J. J. Mccarthy, Richard W TsikaAbstract:The DNA regulatory element(s) involved in beta-myosin heavy chain (beta-MHC) induction by the physiological stimulus of Mechanical Overload have not been identified as yet. To delineate regulatory sequences that are required for Mechanical Overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcription start site (+1). Mechanically Overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene beta 293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2- to 2.5-fold) muscles by Mechanical Overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the Overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated by Mechanical Overload in fast- and slow-twitch muscles.
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Induction of beta-MHC transgene in Overloaded skeletal muscle is not eliminated by mutation of conserved elements.
American Journal of Physiology-Cell Physiology, 1996Co-Authors: G Tsika, J L Wiedenman, I Rivera-rivera, L Gao, K Sheriff-carter, J. J. Mccarthy, Richard W TsikaAbstract:Mechanical Overload leads to hypertrophy, increased type I fiber composition, and beta-myosin heavy chain (beta-MHC) induction in the fast-twitch plantaris muscle. To better understand the mechanism(s) involved in beta-MHC induction, we have examined inducible expression of transgenes carrying the simultaneous mutation of three DNA regulatory subregions [muscle CAT (MCAT), C-rich, and beta e3] in the context of either 5,600-base pair (bp; beta 5.6mut3) or 600-bp (beta 0.6mut3) beta-MHC promoter in Overloaded plantaris muscles of transgenic mice. Protein extract from Mechanically Overloaded plantaris muscle of mice, harboring either mutant transgene beta 5.6mut3 or beta 0.6mut3, showed an unexpected 2.8- to 4.5-fold increase in chloramphenicol acetyltransferase (CAT) specific activity relative to their respective controls. Similar results were obtained with wild-type (wt) beta-MHC transgenes (beta 5.6wt, beta 0.6wt). Histochemical staining for both myofibrillar ATPase and CAT activity and CAT immunohistochemistry revealed a striking increase in type I fibers and that CAT expression was restricted to these fibers in Overloaded plantaris muscle of beta 5.6mut3 transgenic mice. Our transgenic data suggest that beta-MHC transgenes, and perhaps the endogenous beta-MHC gene, are induced by Mechanical Overload via a mechanism(s) that does not exclusively require the MCAT, C-rich, or beta e3 subregions.
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Beta-MHC and SMLC1 transgene induction in Overloaded skeletal muscle of transgenic mice
American Journal of Physiology-Cell Physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, X Wang, L Y Kwan, Richard W TsikaAbstract:The hypertrophic responses of white fast-twitch muscle to Mechanical Overload has been investigated using transgenic mice. After 7 wk of Overload, endogenous beta-myosin heavy chain (MHC) and slow ...
L Gao - One of the best experts on this subject based on the ideXlab platform.
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Muscle-specific and inducible expression of 293-base pair beta-myosin heavy chain promoter in transgenic mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, J. J. Mccarthy, Richard W TsikaAbstract:The DNA regulatory element(s) involved in beta-myosin heavy chain (beta-MHC) induction by the physiological stimulus of Mechanical Overload have not been identified as yet. To delineate regulatory sequences that are required for Mechanical Overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcription start site (+1). Mechanically Overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene beta 293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2- to 2.5-fold) muscles by Mechanical Overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the Overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated by Mechanical Overload in fast- and slow-twitch muscles.
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Induction of beta-MHC transgene in Overloaded skeletal muscle is not eliminated by mutation of conserved elements.
American Journal of Physiology-Cell Physiology, 1996Co-Authors: G Tsika, J L Wiedenman, I Rivera-rivera, L Gao, K Sheriff-carter, J. J. Mccarthy, Richard W TsikaAbstract:Mechanical Overload leads to hypertrophy, increased type I fiber composition, and beta-myosin heavy chain (beta-MHC) induction in the fast-twitch plantaris muscle. To better understand the mechanism(s) involved in beta-MHC induction, we have examined inducible expression of transgenes carrying the simultaneous mutation of three DNA regulatory subregions [muscle CAT (MCAT), C-rich, and beta e3] in the context of either 5,600-base pair (bp; beta 5.6mut3) or 600-bp (beta 0.6mut3) beta-MHC promoter in Overloaded plantaris muscles of transgenic mice. Protein extract from Mechanically Overloaded plantaris muscle of mice, harboring either mutant transgene beta 5.6mut3 or beta 0.6mut3, showed an unexpected 2.8- to 4.5-fold increase in chloramphenicol acetyltransferase (CAT) specific activity relative to their respective controls. Similar results were obtained with wild-type (wt) beta-MHC transgenes (beta 5.6wt, beta 0.6wt). Histochemical staining for both myofibrillar ATPase and CAT activity and CAT immunohistochemistry revealed a striking increase in type I fibers and that CAT expression was restricted to these fibers in Overloaded plantaris muscle of beta 5.6mut3 transgenic mice. Our transgenic data suggest that beta-MHC transgenes, and perhaps the endogenous beta-MHC gene, are induced by Mechanical Overload via a mechanism(s) that does not exclusively require the MCAT, C-rich, or beta e3 subregions.
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Beta-MHC and SMLC1 transgene induction in Overloaded skeletal muscle of transgenic mice
American Journal of Physiology-Cell Physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, X Wang, L Y Kwan, Richard W TsikaAbstract:The hypertrophic responses of white fast-twitch muscle to Mechanical Overload has been investigated using transgenic mice. After 7 wk of Overload, endogenous beta-myosin heavy chain (MHC) and slow ...
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Beta-MHC and SMLC1 transgene induction in Overloaded skeletal muscle of transgenic mice.
The American journal of physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, X Wang, L Y Kwan, R W TsikaAbstract:The hypertrophic responses of white fast-twitch muscle to Mechanical Overload has been investigated using transgenic mice. After 7 wk of Overload, endogenous beta-myosin heavy chain (MHC) and slow myosin light chain 1 and 2 (SMLC1, SMLC2) protein were increased in the Overloaded plantaris (OP) muscle compared with sham-operated control plantaris (CP)muscle. Concurrently, the levels of endogenous beta-MHC, SMLC1, SMLC2, and cardiac/slow troponin C (CTnC) mRNA transcripts were significantly increased in OP muscles, whereas skeletal troponin C (sTnC) mRNA transcript levels decreased. As an initial attempt to locate DNA sequence(s) that governs beta-MHC induction in response to Mechanical Overload, multiple independent transgenic lines harboring four different human beta-MHC transgenes (beta 1286, beta 988, beta 450, beta 141) were generated. Except for transgene beta 141, muscle-specific expression and induction (3- to 22-fold) in OP muscles were observed by measuring chloramphenicol acetyltransferase activity (CAT assay). Induction of a SMLC1 transgene (3920SMLC1) in OP muscles was also observed. Collectively, these in vivo data provide evidence that 1) a Mechanical Overload inducible element(s) is located between nucleotides -450 and +120 of the human beta-MHC transgene, 2) 3,900 bp of 5' sequence is sufficient to confer Mechanical Overload induction of a SMLC1 transgene, and 3) the increased expression of slow/type I isomyosin (beta-MHC, SMLC1, SMLC2) in response to Mechanical Overload is regulated, in part, transcriptionally.
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M-creatine kinase gene expression in Mechanically Overloaded skeletal muscle of transgenic mice.
American Journal of Physiology-Cell Physiology, 1995Co-Authors: Richard W Tsika, S. D. Hauschka, L GaoAbstract:The molecular pathways and regulatory molecules that underlie changes in gene transcription during Mechanical Overload of skeletal muscle remain obscure. To better understand this process, we have examined mouse muscle creatine kinase (MCK) gene expression in Mechanically Overloaded plantaris (OP) muscle of transgenic and nontransgenic mice. Northern blot analysis revealed that endogenous MCK-specific mRNA transcripts were decreased 150% in the OP muscles after 6 wk. To identify the MCK gene regions involved in the response to Mechanical Overload, three different mouse MCKCAT transgenes were studied by measuring chloramphenicol acetyltransferase (CAT assays) activity in OP and sham-operated (control plantaris) muscles. Mouse lines carrying (+enh206)117MCKCAT and -1256MCKCAT transgenes exhibited 30 and 40% lower CAT levels, whereas two mouse lines carrying -3300MCKCAT transgenes exhibited average decreases of 430%. Nearly identical results, including measurements of exogenous CAT mRNA, were obtained 2 days postOverload. Six weeks or 2 days of Mechanical Overload led to an average decrease in MM-CK isoprotein of 140%. These data provide evidence that Mechanical Overload induces changes in MCK gene expression that appear to be regulated by at least two portions of the MCK gene: the 206 base pair 5' enhancer and the -3,300 to -1,257 region.
Martin Valtierra-rodriguez - One of the best experts on this subject based on the ideXlab platform.
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Thermal-Impact-Based Protection of Induction Motors Under Voltage Unbalance Conditions
IEEE Transactions on Energy Conversion, 2018Co-Authors: Jose L. Gonzalez-cordoba, Roque Alfredo Osornio-rios, David Granados-lieberman, Rene De Jesus Romero-troncoso, Martin Valtierra-rodriguezAbstract:Voltage unbalance and Mechanical Overload generate negative effects on induction motors, producing thermal damages in the stator insulation and a reduction of the motor lifetime. In this regard, the development of protection devices is crucial as they can help to maintain the integrity of the motor and avoid irreversible damages such as insulation system breakdown, short-circuits, and so on. In this work, a methodology to obtain a time-protection model for induction motors from voltage unbalance is presented. The methodology is based on the thermal impact on the motor produced by Mechanical Overload and voltage unbalance conditions. In general, it consists of the following steps: i) induce in the motor different Overloads and voltage unbalance levels and monitor their thermal profiles at the stator winding, ii) obtain the time–Overload curve of the motor, iii) determine both the thermal level according to both the time-Overload curve and the Overload thermal profile, and iv) estimate the parameters of the time-unbalance model using both the thermal level obtained and the unbalance thermal profiles. The model is validated through its implementation in an online protection scheme, the results show a similar behavior between Overload and unbalance protections in the safe thermal level defined by the protection models. The protection scheme is carried out over a 750 W three-phase induction motor under different Overload and voltage unbalance operating conditions.
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Correlation Model Between Voltage Unbalance and Mechanical Overload Based on Thermal Effect at the Induction Motor Stator
IEEE Transactions on Energy Conversion, 2017Co-Authors: Jose L. Gonzalez-cordoba, Roque Alfredo Osornio-rios, David Granados-lieberman, Rene De Jesus Romero-troncoso, Martin Valtierra-rodriguezAbstract:Overheating is a negative effect that induction motors suffer under either Mechanical or electrical anomalous conditions, which can decrement the motors' useful life or produce catastrophic damage. In this sense, a new approach for assisting in the analysis and solution of problems related to overheating in induction motors is the correlation of thermal effects between the abovementioned conditions. In this study, a methodology for the experimental extraction of mathematical models that correlate the thermal effect on the induction motor stator due to voltage unbalance and Mechanical Overload is developed. In general, the proposed methodology is based on thermal gradients at different points of an induction motor stator. These thermal gradients are generated from either voltage unbalance or Mechanical Overload. For voltage unbalance estimation, the definitions of IEEE standard 141, IEEE standard 1159, and NEMA norm are considered. The correlation models are carried out and validated experimentally on a three-phase induction motor of 746 W (1 hp). Results demonstrate effectiveness in the correlation at different stator points of both variables: unbalance voltage and Mechanical Overload.
J L Wiedenman - One of the best experts on this subject based on the ideXlab platform.
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Muscle-specific and inducible expression of 293-base pair beta-myosin heavy chain promoter in transgenic mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, J. J. Mccarthy, Richard W TsikaAbstract:The DNA regulatory element(s) involved in beta-myosin heavy chain (beta-MHC) induction by the physiological stimulus of Mechanical Overload have not been identified as yet. To delineate regulatory sequences that are required for Mechanical Overload induction of the beta-MHC gene, transgenic mouse lines were generated that harbor transgenes containing serial deletions of the human beta-MHC promoter to nucleotides -293 (beta 293), -201 (beta 201), and -141 (beta 141) from the transcription start site (+1). Mechanically Overloaded adult plantaris and soleus muscles contained 11- and 1.9-fold increases, respectively, in endogenous beta-MHC-specific mRNA transcripts (Northern blot) compared with sham-operated controls. Expression assays (chloramphenicol acetyltransferase specific activity) revealed that only transgene beta 293 expression was muscle specific in both fetal and adult mice and was induced in the plantaris (10- to 27-fold) and soleus (2- to 2.5-fold) muscles by Mechanical Overload. Histochemical staining for myosin adenosinetriphosphatase activity revealed a fiber-type transition of type II to type I in the Overloaded plantaris and soleus muscles. These transgenic data suggest that sequences located between nucleotides -293 and +120 may be sufficient to regulate the endogenous beta-MHC gene in response to developmental signals and to the physiological signals generated by Mechanical Overload in fast- and slow-twitch muscles.
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Induction of beta-MHC transgene in Overloaded skeletal muscle is not eliminated by mutation of conserved elements.
American Journal of Physiology-Cell Physiology, 1996Co-Authors: G Tsika, J L Wiedenman, I Rivera-rivera, L Gao, K Sheriff-carter, J. J. Mccarthy, Richard W TsikaAbstract:Mechanical Overload leads to hypertrophy, increased type I fiber composition, and beta-myosin heavy chain (beta-MHC) induction in the fast-twitch plantaris muscle. To better understand the mechanism(s) involved in beta-MHC induction, we have examined inducible expression of transgenes carrying the simultaneous mutation of three DNA regulatory subregions [muscle CAT (MCAT), C-rich, and beta e3] in the context of either 5,600-base pair (bp; beta 5.6mut3) or 600-bp (beta 0.6mut3) beta-MHC promoter in Overloaded plantaris muscles of transgenic mice. Protein extract from Mechanically Overloaded plantaris muscle of mice, harboring either mutant transgene beta 5.6mut3 or beta 0.6mut3, showed an unexpected 2.8- to 4.5-fold increase in chloramphenicol acetyltransferase (CAT) specific activity relative to their respective controls. Similar results were obtained with wild-type (wt) beta-MHC transgenes (beta 5.6wt, beta 0.6wt). Histochemical staining for both myofibrillar ATPase and CAT activity and CAT immunohistochemistry revealed a striking increase in type I fibers and that CAT expression was restricted to these fibers in Overloaded plantaris muscle of beta 5.6mut3 transgenic mice. Our transgenic data suggest that beta-MHC transgenes, and perhaps the endogenous beta-MHC gene, are induced by Mechanical Overload via a mechanism(s) that does not exclusively require the MCAT, C-rich, or beta e3 subregions.
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Beta-MHC and SMLC1 transgene induction in Overloaded skeletal muscle of transgenic mice
American Journal of Physiology-Cell Physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, X Wang, L Y Kwan, Richard W TsikaAbstract:The hypertrophic responses of white fast-twitch muscle to Mechanical Overload has been investigated using transgenic mice. After 7 wk of Overload, endogenous beta-myosin heavy chain (MHC) and slow ...
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Beta-MHC and SMLC1 transgene induction in Overloaded skeletal muscle of transgenic mice.
The American journal of physiology, 1996Co-Authors: J L Wiedenman, I Rivera-rivera, D Vyas, G Tsika, L Gao, K Sheriff-carter, X Wang, L Y Kwan, R W TsikaAbstract:The hypertrophic responses of white fast-twitch muscle to Mechanical Overload has been investigated using transgenic mice. After 7 wk of Overload, endogenous beta-myosin heavy chain (MHC) and slow myosin light chain 1 and 2 (SMLC1, SMLC2) protein were increased in the Overloaded plantaris (OP) muscle compared with sham-operated control plantaris (CP)muscle. Concurrently, the levels of endogenous beta-MHC, SMLC1, SMLC2, and cardiac/slow troponin C (CTnC) mRNA transcripts were significantly increased in OP muscles, whereas skeletal troponin C (sTnC) mRNA transcript levels decreased. As an initial attempt to locate DNA sequence(s) that governs beta-MHC induction in response to Mechanical Overload, multiple independent transgenic lines harboring four different human beta-MHC transgenes (beta 1286, beta 988, beta 450, beta 141) were generated. Except for transgene beta 141, muscle-specific expression and induction (3- to 22-fold) in OP muscles were observed by measuring chloramphenicol acetyltransferase activity (CAT assay). Induction of a SMLC1 transgene (3920SMLC1) in OP muscles was also observed. Collectively, these in vivo data provide evidence that 1) a Mechanical Overload inducible element(s) is located between nucleotides -450 and +120 of the human beta-MHC transgene, 2) 3,900 bp of 5' sequence is sufficient to confer Mechanical Overload induction of a SMLC1 transgene, and 3) the increased expression of slow/type I isomyosin (beta-MHC, SMLC1, SMLC2) in response to Mechanical Overload is regulated, in part, transcriptionally.
Shu Chien - One of the best experts on this subject based on the ideXlab platform.
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correction corrigendum role of excessive autophagy induced by Mechanical Overload in vein graft neointima formation prediction and prevention
Scientific Reports, 2016Co-Authors: Yaju Chang, Hui Chun Huang, Yuan Yu Hsueh, Shaowei Wang, Chih Han Chang, Ming Jer Tang, Shyhhau Wang, K K Shung, Shu ChienAbstract:Scientific Reports 6: Article number: 22147; published online: 26 February 2016; updated: 14 November 2016 The original version of this Article contained errors in the affiliations. ‘Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan’ was incomplete, and now reads: ‘Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan’
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role of excessive autophagy induced by Mechanical Overload in vein graft neointima formation prediction and prevention
Scientific Reports, 2016Co-Authors: Yaju Chang, Hui Chun Huang, Yuan Yu Hsueh, Shaowei Wang, Chih Han Chang, Ming Jer Tang, Shyhhau Wang, K K Shung, Shu ChienAbstract:Little is known regarding the interplays between the Mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large Mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.