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F. C. Howarth - One of the best experts on this subject based on the ideXlab platform.
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different profile of mrna expression in sinoatrial node from streptozotocin induced diabetic rat
PLOS ONE, 2016Co-Authors: Zannatul Ferdous, K. Parekh, Petrilla Jayaprakash, Thomas E. Adrian, Muhammad Anwar Qureshi, Annie John, Murat Oz, Haider Raza, Halina Dobrzynski, F. C. HowarthAbstract:Background Experiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)–induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart. Methodology/Principal Findings Heart rate was measured in isolated perfused heart with an extraCellular suction electrode. Expression of mRNA encoding a variety of interCellular proteins, intraCellular Ca2+-Transport and regulatory proteins, Cell Membrane Transport proteins and calcium, sodium and potassium channel proteins were measured in SAN and right atrial (RA) biopsies using real-time reverse transcription polymerase chain reaction techniques. Heart rate was lower in STZ (203±7 bpm) compared to control (239±11 bpm) rat. Among many differences in the profile of mRNA there are some worthy of particular emphasis. Expression of genes encoding some proteins were significantly downregulated in STZ-SAN: calcium channel, Cacng4 (7-fold); potassium channel, Kcnd2 whilst genes encoding some other proteins were significantly upregulated in STZ-SAN: gap junction, Gjc1; Cell Membrane Transport, Slc8a1, Trpc1, Trpc6 (4-fold); intraCellular Ca2+-Transport, Ryr3; calcium channel Cacna1g, Cacna1h, Cacnb3; potassium channels, Kcnj5, Kcnk3 and natriuretic peptides, Nppa (5-fold) and Nppb (7-fold). Conclusions/Significance Collectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function.
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P400Effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in Goto-Kakizaki type 2 diabetic rat heart
Cardiovascular Research, 2014Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, E El Nebrisi, Petrilla Jayaprakash, Thomas E. AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity which in turn is a risk factor for development of type 2 diabetes mellitus. The effects of a sucrose-enriched diet on the pattern of gene expression, contraction and calcium Transport in the Goto-Kakizaki (GK) type 2 diabetic rat heart have been investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3, Mylpf), interCellular proteins (Gja4), Cell Membrane Transport (Atp1b1), calcium channels (Cacna1c, Cacna1g, Cacnb1), potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared to Control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3, Tnn2), interCellular proteins (Gja1, Gja4), intraCellular calcium Transport (Atp2a1, Ryr2), Cell Membrane Transport (Atp1a2, Atp1b1), potassium channel (Kcnj2, Kcnj8) proteins were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in Control/Sucrose compared to Control rats. Genes encoding cardiac muscle proteins (Myh7), potassium channel (Kcnj11) proteins were downregulated in GK/Sucrose compared to Control rats. Amplitude of shortening was reduced in myocytes from Control/Sucrose compared to Control and in GK/Sucrose compared to GK rats. Amplitude of the calcium transient was increased in myocytes from Control/Sucrose compared to Control and decreased in GK/Sucrose compared to GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intraCellular calcium Transport in ventricular myocytes from GK type 2 diabetic and Control rats fed a sucrose-enriched diet.
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effects of a sucrose enriched diet on the pattern of gene expression contraction and ca2 Transport in goto kakizaki type 2 diabetic rat heart
Experimental Physiology, 2014Co-Authors: E M Gaber, K. Parekh, M. A. Qureshi, Petrilla Jayaprakash, Thomas E. Adrian, F. C. HowarthAbstract:New Findings What is the central question of this study? Poor diet is a risk factor for development of type 2 diabetes mellitus and its associated complications. In this study, the effects of sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in type 2 diabetic heart are explored. What is the main finding and its importance? The altered pattern of gene expression in type 2 diabetic hearts was further altered in diabetic and control rats that received a sucrose-enriched diet, and these alterations were associated with changes in ventricular myocyte shortening and Ca2+ Transport. There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in the Goto–Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), interCellular proteins (Gja4), Cell Membrane Transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), interCellular proteins (Gja1 and Gja4), intraCellular Ca2+ Transport (Atp2a1 and Ryr2), Cell Membrane Transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control–sucrose group compared with control rats and in the GK–sucrose group compared with GK rats. The amplitude of the Ca2+ transient was increased in myocytes from control–sucrose compared with control rats and decreased in GK–sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intraCellular Ca2+ Transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet.
Thomas E. Adrian - One of the best experts on this subject based on the ideXlab platform.
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different profile of mrna expression in sinoatrial node from streptozotocin induced diabetic rat
PLOS ONE, 2016Co-Authors: Zannatul Ferdous, K. Parekh, Petrilla Jayaprakash, Thomas E. Adrian, Muhammad Anwar Qureshi, Annie John, Murat Oz, Haider Raza, Halina Dobrzynski, F. C. HowarthAbstract:Background Experiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)–induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart. Methodology/Principal Findings Heart rate was measured in isolated perfused heart with an extraCellular suction electrode. Expression of mRNA encoding a variety of interCellular proteins, intraCellular Ca2+-Transport and regulatory proteins, Cell Membrane Transport proteins and calcium, sodium and potassium channel proteins were measured in SAN and right atrial (RA) biopsies using real-time reverse transcription polymerase chain reaction techniques. Heart rate was lower in STZ (203±7 bpm) compared to control (239±11 bpm) rat. Among many differences in the profile of mRNA there are some worthy of particular emphasis. Expression of genes encoding some proteins were significantly downregulated in STZ-SAN: calcium channel, Cacng4 (7-fold); potassium channel, Kcnd2 whilst genes encoding some other proteins were significantly upregulated in STZ-SAN: gap junction, Gjc1; Cell Membrane Transport, Slc8a1, Trpc1, Trpc6 (4-fold); intraCellular Ca2+-Transport, Ryr3; calcium channel Cacna1g, Cacna1h, Cacnb3; potassium channels, Kcnj5, Kcnk3 and natriuretic peptides, Nppa (5-fold) and Nppb (7-fold). Conclusions/Significance Collectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function.
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P400Effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in Goto-Kakizaki type 2 diabetic rat heart
Cardiovascular Research, 2014Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, E El Nebrisi, Petrilla Jayaprakash, Thomas E. AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity which in turn is a risk factor for development of type 2 diabetes mellitus. The effects of a sucrose-enriched diet on the pattern of gene expression, contraction and calcium Transport in the Goto-Kakizaki (GK) type 2 diabetic rat heart have been investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3, Mylpf), interCellular proteins (Gja4), Cell Membrane Transport (Atp1b1), calcium channels (Cacna1c, Cacna1g, Cacnb1), potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared to Control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3, Tnn2), interCellular proteins (Gja1, Gja4), intraCellular calcium Transport (Atp2a1, Ryr2), Cell Membrane Transport (Atp1a2, Atp1b1), potassium channel (Kcnj2, Kcnj8) proteins were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in Control/Sucrose compared to Control rats. Genes encoding cardiac muscle proteins (Myh7), potassium channel (Kcnj11) proteins were downregulated in GK/Sucrose compared to Control rats. Amplitude of shortening was reduced in myocytes from Control/Sucrose compared to Control and in GK/Sucrose compared to GK rats. Amplitude of the calcium transient was increased in myocytes from Control/Sucrose compared to Control and decreased in GK/Sucrose compared to GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intraCellular calcium Transport in ventricular myocytes from GK type 2 diabetic and Control rats fed a sucrose-enriched diet.
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effects of a sucrose enriched diet on the pattern of gene expression contraction and ca2 Transport in goto kakizaki type 2 diabetic rat heart
Experimental Physiology, 2014Co-Authors: E M Gaber, K. Parekh, M. A. Qureshi, Petrilla Jayaprakash, Thomas E. Adrian, F. C. HowarthAbstract:New Findings What is the central question of this study? Poor diet is a risk factor for development of type 2 diabetes mellitus and its associated complications. In this study, the effects of sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in type 2 diabetic heart are explored. What is the main finding and its importance? The altered pattern of gene expression in type 2 diabetic hearts was further altered in diabetic and control rats that received a sucrose-enriched diet, and these alterations were associated with changes in ventricular myocyte shortening and Ca2+ Transport. There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in the Goto–Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), interCellular proteins (Gja4), Cell Membrane Transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), interCellular proteins (Gja1 and Gja4), intraCellular Ca2+ Transport (Atp2a1 and Ryr2), Cell Membrane Transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control–sucrose group compared with control rats and in the GK–sucrose group compared with GK rats. The amplitude of the Ca2+ transient was increased in myocytes from control–sucrose compared with control rats and decreased in GK–sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intraCellular Ca2+ Transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet.
Yizhou Wang - One of the best experts on this subject based on the ideXlab platform.
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Optimized Protocol for OnGuard2 Software in Studying Guard Cell Membrane Transport and Stomatal Physiology.
Frontiers in plant science, 2020Co-Authors: Sehar Shafaque, Mengmeng Rui, Ziyi Zhu, Fangbing Cao, Yizhou WangAbstract:Stomata are key innovation in plants that drives the global carbon and water cycle. In the past few decades, many stomatal models have been developed for studying gas exchange, photosynthesis, and transpirational characteristics of plants, but they provide limited information on stomatal mechanisms at the molecular and Cellular levels. Quantitative mathematical modeling offers an effective in silico approach to explore the link between microscopic Transporter functioning and the macroscopic stomatal characteristics. As a first step, a dynamic system model based on the guard Cell Membrane Transport system was developed and encoded in the OnGuard software. This software has already generated a wealth of testable predictions and outcomes sufficient to guide phenotypic and mutational studies. It has a user-friendly interface, which can be easily accessed by researchers to manipulate the key elements and parameters in the system for guard Cell simulation in plants. To promote the adoption of this OnGuard application, here we outline a standard protocol that will enable users with experience in basic plant physiology, Cell biology, and Membrane Transport to advance quickly in learning to use it.
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systems analysis of guard Cell Membrane Transport for enhanced stomatal dynamics and water use efficiency
Plant Physiology, 2014Co-Authors: Yizhou Wang, Adrian Hills, Michael R BlattAbstract:Stomatal transpiration is at the center of a crisis in water availability and crop production that is expected to unfold over the next 20 to 30 years. Global water usage has increased 6-fold in the past 100 years, twice as fast as the human population, and is expected to double again before 2030, driven mainly by irrigation and agriculture. Guard Cell Membrane Transport is integral to controlling stomatal aperture and offers important targets for genetic manipulation to improve crop performance. However, its complexity presents a formidable barrier to exploring such possibilities. With few exceptions, mutations that increase water use efficiency commonly have been found to do so with substantial costs to the rate of carbon assimilation, reflecting the trade-off in CO2 availability with suppressed stomatal transpiration. One approach yet to be explored in detail relies on quantitative systems analysis of the guard Cell. Our deep knowledge of Transport and homeostasis in these Cells gives real substance to the prospect for reverse engineering of stomatal responses, using in silico design in directing genetic manipulation for improved water use and crop yields. Here we address this problem with a focus on stomatal kinetics, taking advantage of the OnGuard software and models of the stomatal guard Cell recently developed for exploring stomatal physiology. Our analysis suggests that manipulations of single Transporter populations are likely to have unforeseen consequences. Channel gating, especially of the dominant K+ channels, appears the most favorable target for experimental manipulation.
Samuel Refetoff - One of the best experts on this subject based on the ideXlab platform.
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prenatal treatment of thyroid hormone Cell Membrane Transport defect caused by mct8 gene mutation
Thyroid, 2020Co-Authors: Samuel Refetoff, Theodora Pappa, Meredith K Williams, Gisele M Matheus, Xiao Hui Liao, Karen Hansen, Lindsey Nicol, Melinda Pierce, Peter A Blasco, Mandie Wiebers JensenAbstract:Background: Mutations of the thyroid hormone (TH)-specific Cell Membrane Transporter, monocarboxylate Transporter 8 (MCT8), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits. Studies of brain from a 30-week-old MCT8-deficient embryo indicated that brain abnormalities were already present during fetal life. Methods: A carrier woman with an affected male child (MCT8 A252fs268*), pregnant with a second affected male embryo, elected to carry the pregnancy to term. We treated the fetus with weekly 500 μg intra-amniotic instillation of levothyroxine (LT4) from 18 weeks of gestation until birth at 35 weeks. Thyroxine (T4), T3, and thyrotropin (TSH) were measured in the amniotic fluid and maternal serum. Treatment after birth was continued with LT4 and propylthiouracil. Follow-up included brain magnetic resonance imaging (MRI) and neurodevelopmental evaluation, both compared with the untreated brother. Results: During intrauterine life, T4 and T3 in the amniotic fluid were maintained above threefold to twofold the baseline and TSH was suppressed by 80%, while maternal serum levels remained unchanged. At birth, the infant serum T4 was 14.5 μg/dL and TSH 8 mU/L, respectively. MRI at six months of age showed near-normal brain myelination compared with much reduced in the untreated brother. Neurodevelopmental assessment showed developmental quotients in receptive language and problem-solving, and gross motor and fine motor function ranged from 12 to 25 at 31 months in the treated boy and from 1 to 7 at 58 months in the untreated brother. Conclusions: This is the first demonstration that prenatal treatment improved the neuromotor and neurocognitive function in MCT8 deficiency. Earlier treatment with TH analogues that concentrate in the fetus when given to the mother may further rescue the phenotype.
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Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by MCT8 Gene Mutation
Thyroid : official journal of the American Thyroid Association, 2020Co-Authors: Samuel Refetoff, Theodora Pappa, Meredith K Williams, Xiao Hui Liao, Karen Hansen, Lindsey Nicol, Melinda Pierce, Peter A Blasco, M. Gisele Matheus, Mandie Wiebers JensenAbstract:Background: Mutations of the thyroid hormone (TH)-specific Cell Membrane Transporter, monocarboxylate Transporter 8 (MCT8), produce an X-chromosome-linked syndrome of TH deficiency in the brain and...
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Thyroid Hormone Resistance Syndromes
The Thyroid and Its Diseases, 2019Co-Authors: Roy E. Weiss, Samuel RefetoffAbstract:Syndromes with impaired sensitivity to thyroid hormone (TH) include three types of resistance to thyroid hormone (RTH) syndromes (RTHβ, RTHα, and nonTR-RTH) and also include patients with defects in TH Transport into Cells (thyroid hormone Cell Membrane Transport defect, THCMTD) and defects in TH metabolism (thyroid hormone metabolism defect, THMD). The overall goal of this chapter is to discuss the treatment options for patients with various syndromes of impaired sensitivity to TH. These are rare conditions with little or no evidence-based information for the “best” treatment of patients. The first step toward treatment of all of these syndromes is making an accurate diagnosis based on a combination of the clinical presentation and laboratory tests that ultimately requires genetic confirmation. Recognizing the etiology leads to a more logical approach to treatment.
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inherited defects of thyroid hormone Cell Membrane Transport review of recent findings
Current Opinion in Endocrinology Diabetes and Obesity, 2013Co-Authors: Samuel Refetoff, Alexandra M DumitrescuAbstract:PURPOSE OF REVIEW This review summarizes the most significant findings over the last year regarding human and animal models deficient in thyroid hormone Cell-Membrane Transporters (THCMTs). Although several THCMTs have been modelled in genetically engineered mice, the only THCMT defect known in humans is that caused by mutations in the monocarboxylate Transporter 8 (MCT8) gene. RECENT FINDINGS The importance of several amino acid residues has been assessed in vitro to further our understanding on the structure-function of the MCT8. The administration of the thyromimetic compound, diiodothyropropionic acid, has been tested in patients with MCT8 gene mutations, following studies of its use in mice. Another thyroid hormone analogue, 3,3',5,5'-tetraiodothyroacetic acid, was tested in Mct8-deficient mice. The phenotypes of L-type aminoacid Transporter 2 and organic anion Transporting polypeptide 1C1 deficiencies have been studied in mouse models. Mct8/organic anion Transporting polypeptide 1C1 double knockout mice have been shown to manifest neurodevelopmental deficits. Zebrafish is emerging as another vertebrate model that may be useful to study the role of Mct8 in brain development. SUMMARY Studies on the pathogenesis and therapy of MCT8 deficiency are in progress, and new vertebrate models that are suitable to study the neurological consequences of the syndrome are being explored.
K. Parekh - One of the best experts on this subject based on the ideXlab platform.
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different profile of mrna expression in sinoatrial node from streptozotocin induced diabetic rat
PLOS ONE, 2016Co-Authors: Zannatul Ferdous, K. Parekh, Petrilla Jayaprakash, Thomas E. Adrian, Muhammad Anwar Qureshi, Annie John, Murat Oz, Haider Raza, Halina Dobrzynski, F. C. HowarthAbstract:Background Experiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)–induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart. Methodology/Principal Findings Heart rate was measured in isolated perfused heart with an extraCellular suction electrode. Expression of mRNA encoding a variety of interCellular proteins, intraCellular Ca2+-Transport and regulatory proteins, Cell Membrane Transport proteins and calcium, sodium and potassium channel proteins were measured in SAN and right atrial (RA) biopsies using real-time reverse transcription polymerase chain reaction techniques. Heart rate was lower in STZ (203±7 bpm) compared to control (239±11 bpm) rat. Among many differences in the profile of mRNA there are some worthy of particular emphasis. Expression of genes encoding some proteins were significantly downregulated in STZ-SAN: calcium channel, Cacng4 (7-fold); potassium channel, Kcnd2 whilst genes encoding some other proteins were significantly upregulated in STZ-SAN: gap junction, Gjc1; Cell Membrane Transport, Slc8a1, Trpc1, Trpc6 (4-fold); intraCellular Ca2+-Transport, Ryr3; calcium channel Cacna1g, Cacna1h, Cacnb3; potassium channels, Kcnj5, Kcnk3 and natriuretic peptides, Nppa (5-fold) and Nppb (7-fold). Conclusions/Significance Collectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function.
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P400Effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in Goto-Kakizaki type 2 diabetic rat heart
Cardiovascular Research, 2014Co-Authors: F. C. Howarth, K. Parekh, M. A. Qureshi, E El Nebrisi, Petrilla Jayaprakash, Thomas E. AdrianAbstract:There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity which in turn is a risk factor for development of type 2 diabetes mellitus. The effects of a sucrose-enriched diet on the pattern of gene expression, contraction and calcium Transport in the Goto-Kakizaki (GK) type 2 diabetic rat heart have been investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3, Mylpf), interCellular proteins (Gja4), Cell Membrane Transport (Atp1b1), calcium channels (Cacna1c, Cacna1g, Cacnb1), potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared to Control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3, Tnn2), interCellular proteins (Gja1, Gja4), intraCellular calcium Transport (Atp2a1, Ryr2), Cell Membrane Transport (Atp1a2, Atp1b1), potassium channel (Kcnj2, Kcnj8) proteins were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in Control/Sucrose compared to Control rats. Genes encoding cardiac muscle proteins (Myh7), potassium channel (Kcnj11) proteins were downregulated in GK/Sucrose compared to Control rats. Amplitude of shortening was reduced in myocytes from Control/Sucrose compared to Control and in GK/Sucrose compared to GK rats. Amplitude of the calcium transient was increased in myocytes from Control/Sucrose compared to Control and decreased in GK/Sucrose compared to GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intraCellular calcium Transport in ventricular myocytes from GK type 2 diabetic and Control rats fed a sucrose-enriched diet.
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effects of a sucrose enriched diet on the pattern of gene expression contraction and ca2 Transport in goto kakizaki type 2 diabetic rat heart
Experimental Physiology, 2014Co-Authors: E M Gaber, K. Parekh, M. A. Qureshi, Petrilla Jayaprakash, Thomas E. Adrian, F. C. HowarthAbstract:New Findings What is the central question of this study? Poor diet is a risk factor for development of type 2 diabetes mellitus and its associated complications. In this study, the effects of sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in type 2 diabetic heart are explored. What is the main finding and its importance? The altered pattern of gene expression in type 2 diabetic hearts was further altered in diabetic and control rats that received a sucrose-enriched diet, and these alterations were associated with changes in ventricular myocyte shortening and Ca2+ Transport. There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus (T2DM), and cardiovascular disease is the major cause of morbidity and mortality in diabetic patients. A variety of diastolic and systolic dysfunctions have been demonstrated in type 2 diabetic heart. The consumption of sugar-sweetened beverages has been linked to rising rates of obesity, which in turn is a risk factor for development of T2DM. In this study, the effects of a sucrose-enriched diet on the pattern of gene expression, contraction and Ca2+ Transport in the Goto–Kakizaki T2DM rat heart were investigated. Genes encoding cardiac muscle proteins (Myh7, Mybpc3, Myl1, Myl3 and Mylpf), interCellular proteins (Gja4), Cell Membrane Transport (Atp1b1), calcium channels (Cacna1c, Cacna1g and Cacnb1) and potassium channels (Kcnj11) were upregulated and genes encoding potassium channels (Kcnb1) were downregulated in GK compared with control rats. Genes encoding cardiac muscle proteins (Myh6, Mybpc3 and Tnn2), interCellular proteins (Gja1 and Gja4), intraCellular Ca2+ Transport (Atp2a1 and Ryr2), Cell Membrane Transport (Atp1a2 and Atp1b1) and potassium channel proteins (Kcnj2 and Kcnj8) were upregulated and genes encoding cardiac muscle proteins (Myh7) were downregulated in control rats fed sucrose compared with control rats. Genes encoding cardiac muscle proteins (Myh7) and potassium channel proteins (Kcnj11) were downregulated in control and GK rats fed sucrose compared with control and GK rats, respectively. The amplitude of shortening was reduced in myocytes from the control–sucrose group compared with control rats and in the GK–sucrose group compared with GK rats. The amplitude of the Ca2+ transient was increased in myocytes from control–sucrose compared with control rats and decreased in GK–sucrose compared with GK rats. Subtle alterations in the pattern of expression of genes encoding a variety of cardiac muscle proteins are associated with changes in shortening and intraCellular Ca2+ Transport in ventricular myocytes from GK T2DM and control rats fed a sucrose-enriched diet.