Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha- and beta-myosin heavy chain (MHC), the two MHC isoforms expressed in the mammalian heart, differ quantitatively in their enzymatic activities. The MHC composition of the heart can change dramatically in response to numerous stimuli, leading to the hypothesis that changes in cardiac function can be caused by myosin isoform shifts. However, this hypothesis has remained unproven because the stimuli used to generate these shifts are complex and accompanied by many additional physiological changes, including alterations in cardiac mass and geometry. Adult mouse ventricles normally express only alpha-MHC (the faster motor). To determine whether genetic alteration of the MHC isoform composition in the adult mouse heart would result in changes in cardiac chamber mass and contractility, we established transgenic mouse lines that express a Myc-tagged beta-MHC molecule (the slower motor) in adult ventricular tissue, one of which expresses 12% of its myosin as the transgene. There is no evidence of hypertrophy, induction of hypertrophic markers, and no histopathology. Myofibrillar Ca(2+)-activated ATPase activity is decreased by 23%, and Langendorff preparations demonstrate a significant 15% decrease in systolic function in transgenic hearts. These results suggest that even small shifts in the myosin isoform composition of the myocardium can result in physiologically significant changes in cardiac contractility and could be relevant to cardiovascular disease.
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PMID:Expression of the beta (slow)-isoform of MHC in the adult mouse heart causes dominant-negative functional effects. 1066 70

The mouse has been used extensively for generating transgenic animal models to study cardiovascular disease. Recently, a number of transgenic mouse models have been created to investigate the importance of sarcoplasmic reticulum (SR) Ca(2+)transport proteins in cardiac pathophysiology. However, the expression and regulation of cardiac SR Ca(2+)ATPase and other Ca(2+)transport proteins have not been studied in detail in the mouse. In this study, we used multiplex RNase mapping analysis to determine SERCA2, phospholamban (PLB), and Na(+)/Ca(2+)-exchanger (NCX-1) gene expression throughout mouse heart development and in hypo/hyperthyroid animals. Our results demonstrate that the expression of SERCA2 and PLB mRNA increase eight-fold from fetal to adult stages, indicating that SR function increases with heart development. In contrast, the expression of the Na(+)/Ca(2+)-exchanger gene is two-fold higher in fetal heart compared to adult. Our study also makes the important observation that in hypothyroidic hearts the NCX-1 mRNA and protein levels were upregulated, whereas the SERCA2 mRNA/protein levels were downregulated. In hyperthyroidic hearts, however, an opposite response was identified. These findings are important and point out that the expression of NCX-1 is regulated antithetically to that of SERCA2 during heart development and in response to alterations in thyroid hormone levels.
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PMID:The expression of SR calcium transport ATPase and the Na(+)/Ca(2+)Exchanger are antithetically regulated during mouse cardiac development and in Hypo/hyperthyroidism. 1073 44

Elderly individuals experience a disproportionate burden from cardiovascular disease. Global changes in aging will have a significant impact on the future of medical practice. However, most physicians have little formal training in geriatric medicine and sometimes fail to distinguish disease states from normal aging. Increasingly, it is recognised that a sedentary lifestyle may be responsible for a large fraction of the so-called 'age-related' changes in the cardiovascular system. Nonetheless, well characterised changes do occur in most individuals with aging. Loss of myocytes with subsequent hypertrophy of the remaining cells is usually observed. Calcification involving the conduction and valvular apparatus is seen in most elderly individuals and may predispose to the common arrhythmias of old age. Age-related loss of arterial compliance contributes to isolated systolic hypertension and left ventricular hypertrophy. Despite these changes, for the majority of healthy older adults, cardiac output is well maintained in the basal state through use of the Frank-Starling principle, in the setting of reduced early diastolic filling. Myocardial relaxation is slowed in part due to age-related changes in the sarcoplasmic reticulum Ca2+ ATPase pump. Elevated blood levels of catecholamines contribute to desensitisation to noradrenergic stimulation and this is associated with an age-related decline in maximum achievable heart rate. Changes in the baroreceptor reflex function and decreased sodium conservation may predispose some individuals to orthostatic and postprandial hypotension. The aetiology of cardiovascular aging is under intense study. The most likely mechanisms involve the result of cumulative damage mediated through a variety of insults. Oxidative stress, non-enzymatic glycation, inflammation and changes in cardiovascular gene expression all seem to influence cardiovascular aging. The benefits of exercise continue to be discovered. Endurance-type training has been shown to have a dramatic impact on parameters of cardiovascular aging. Favourable effects are seen in maximum oxygen consumption, diastolic filling, relaxation and arterial stiffness. Some changes such as the maximum heart rate response do not appear to change with conditioning. Pharmacotherapy may afford the opportunity to influence the aging process. Drugs that can reduce age-associated arterial stiffness, cardiac fibrosis and ventricular hypertrophy should prove useful. Antioxidants continue to be a topic of great interest and require more study. Despite some well described changes with aging, most elderly individuals maintain the opportunity for improved cardiovascular function through conditioning. Early recognition and treatment of diseases that are distinguishable from normal aging, including hypertension and atherosclerosis, together with preventive efforts, should reduce the predicted trends in cardiovascular morbidity and mortality among the aged.
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PMID:Clinical implications of physiological changes in the aging heart. 1134 74

Estrogen status is known to affect the incidence of cardiovascular disease. Experiments were designed to prove the influences of in vivo estrogen manipulations on vascular hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF), and to explore the possible mechanism contributing to the altered EDHF responses in estrogen-deficient states. Mesenteric arteries with intact endothelium were isolated from sham-operated (control), ovariectomized (OVX), or OVX with 17beta-estradiol replacement (OVX + E ) female rats. In the presence of apamin and charybdotoxin, there was no difference between groups in relaxations to the Ca ionophore A23187 and the endoplasmic reticulum Ca -adenosine triphosphatase inhibitor cyclopiazonic acid (CPA). However, N -nitro-L-arginine produced a marked decrease in A23187- and CPA-induced relaxations in OVX compared with control and OVX + E arteries. In control arteries, A23187 and CPA elicited membrane hyperpolarization in a sustained manner. In contrast, A23187 produced only a small and transient hyperpolarizing effect in OVX arteries. OVX also greatly attenuated the sustained pattern of hyperpolarization to CPA. Such changes in hyperpolarizations were not seen in OVX + E arteries. The EDHF-mediated relaxant and hyperpolarizing responses of control arteries to A23187 and CPA were significantly inhibited by the gap junction inhibitor 18 alpha-glycyrrhetinic acid. Immunohistochemical examination for connexin-43 showed that the expression was abundant along the endothelial layer in control and OVX + E arteries, while being much less in OVX arteries. It was concluded that estrogen deficiency specifically impairs EDHF-mediated vascular actions. This may be partly explained by the reduced expression of connexin-43, a protein molecule that could form myoendothelial gap junction channels.
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PMID:Ovariectomy attenuates hyperpolarization and relaxation mediated by endothelium-derived hyperpolarizing factor in female rat mesenteric artery: a concomitant decrease in connexin-43 expression. 1245 28

It is commonly known that consumption of foods and beverages rich in polyphenols is associated with a lower incidence of cardiovascular disease. The purpose of this study was to assess whether the application of red wine polyphenols influences the kinetic properties of renal Na(+),K(+)-ATPase in rats in which hypertension has been experimentally induced by the nitric oxide synthase inhibitor L-NAME. Treatment with polyphenols during the recovery from hypertension to normotension resulted in the complete revival of the functional properties of the Na(+),K(+)-ATPase, as indicated by the total restoration of K(m), K(Na) (concentration of Na(+) necessary to achieve half-maximal reaction velocity) and V(max) for enzyme activation by ATP and/or Na(+) to pre-hypertension values. Two positive effects of polyphenols during the recovery period are indicated: a restoration of the affinity of the ATP and Na(+) binding sites to control values and a probable increase in the number of Na(+),K(+)-ATPase molecules to a level comparable to that in control conditions, as suggested by the complete renewal of V(max).
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PMID:Effect of polyphenolic compounds on the renal Na(+),K(+)-ATPase during the restoration of normotension after experimentally induced hypertension in rats. 1286 34

1. Taurine and homocysteine are metabolites of methionine. Hyperhomocysteinaemia is one of the risk factors for cardiovascular disease. Although taurine may be a cardiovascular cytoprotective substance, we hypothesized that it may antagonize the effects of homocysteine on myocardial mitochondrial function. 2. We studied the effects of taurine and homocysteine on [(45)Ca] uptake, Ca(2+)-ATPase activity and generation of hydrogen peroxide and superoxide anions in vitro in rat isolated myocardial mitochondria. 3. Results showed that the inhibition of mitochondrial [(45)Ca] uptake by homocysteine (0.1, 0.5 and 1.0 mmol/L) was concentration dependent. Taurine (5, 10 and 20 mmol/L) promoted [(45)Ca] uptake in a concentration-dependent manner, as well as concentration dependently reducing the homocysteine (0.5 mmol/L)-induced inhibition of mitochondrial [(45)Ca] uptake. 4. Homocysteine significantly inhibited mitochondrial Ca(2+)-ATPase activity, whereas taurine had a diphasic action on this activity. Taurine, at 5 and 10 mmol/L, increased Ca(2+)-ATPase activity (P < 0.01), but 20 mmol/L taurine inhibited Ca(2+)-ATPase activity (P < 0.05). Taurine attenuated the inhibitory effect of homocysteine on Ca(2+)-ATPase activity. 5. Homocysteine stimulated the generation of hydrogen peroxide and superoxide anions. Taurine had no effect on the generation of the anions, but inhibited their homocysteine-stimulated generation. 6. These results indicate that taurine and homocysteine have opposite effects in myocardial mitochondria with regard to [(45)Ca] uptake, Ca(2+)-ATPase activity and the generation of hydrogen peroxide and superoxide anions. Our results may show an important mechanism for the cardiovascular protective effects of taurine.
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PMID:Effects of taurine and homocysteine on calcium homeostasis and hydrogen peroxide and superoxide anions in rat myocardial mitochondria. 1505 20

To study the molecular mechanism of action of ligustrazine, a low-density oligonucleotide microarray for cardiovascular disease-related genes, was constructed, and the preparation and hybridization protocols were optimized. Under the optimized conditions, the molecular mechanism of action of ligustrazine was analyzed with human umbilical vein endothelial cells. After 4 h of treatment with 100 microg/ml of ligustrazine, calcium-ATPase gene, sodium channel gene, P450c11 gene in human umbilical vein endothelial cells were up-regulated while apolipoprotein C-III gene was down-regulated. The results were shown to be reproducible. RT-PCR confirmed the results from microarray. These results suggest that ligustrazine may act on the function of human umbilical vein endothelial cells via modulating the expressions of cardiovascular disease-related genes. This also demonstrates the use of oligonucleotide microarray technology as an approach to studying targets of active components of Traditional Chinese Medicine.
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PMID:Preparation of cardiovascular disease-related genes microarray and its application in exploring ligustrazine-induced changes in endothelial gene expression. 1552 Apr 97

Myotonic dystrophy (DM) is caused by a CTG expansion in the 3'-untranslated region of a protein kinase gene (DMPK). Cardiovascular disease is one of the most prevalent causes of death in DM patients. Electrophysiological studies in cardiac muscles from DM patients and from DMPK(-/-) mice suggested that DMPK is critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity. However, there are no data regarding the molecular signaling pathways involved in DM heart failure. Here we show that DMPK expression in cardiac myocytes is highly enriched in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and phospholamban (PLN), a muscle-specific SR Ca(2+)-ATPase (SERCA2a) inhibitor. Coimmunoprecipitation studies showed that DMPK and PLN can physically associate. Furthermore, purified wild-type DMPK, but not a kinase-deficient mutant (K110A DMPK), phosphorylates PLN in vitro. Subsequent studies using the DMPK(-/-) mice demonstrated that PLN is hypo-phosphorylated in SR vesicles from DMPK(-/-) mice compared with wild-type mice both in vitro and in vivo. Finally, we show that Ca(2+) uptake in SR is impaired in ventricular homogenates from DMPK(-/-) mice. Together, our data suggest the existence of a novel regulatory DMPK pathway for cardiac contractility and provide a molecular mechanism for DM heart pathology.
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PMID:Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum. 1559 48

This article includes historical sketch of magnesium research, basic researches on effect of magnesium on cardiovascular disease, practical researches (including clinical studies) on relationship between magnesium intake and cardiovascular disease and current status of intake amount of magnesium in Japanese estimated by the national nutrition survey in Japan, 2002. Basic studies revealed the mechanism that magnesium deficiency may decrease ATPase, leading to increase in intracellular calcium of blood vessels, and then the vasoconstriction occurs in cardiovascular system. Clinical studies clarified that magnesium levels in serum decreased significantly in patients with ischemic heart disease. The National Nutrition Survey in Japan revealed that intake amount of magnesium of people for 15 - 49 year male and female were below the recommended dietary allowance of magnesium in Japan.
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PMID:[Magnesium intake and cardiovascular disease]. 1569 52

The generation of reactive oxygen species and other free radicals during metabolism is a necessary and normal process that ideally is compensated for by an elaborate endogenous antioxidant system. However, due to many environmental, lifestyle, and pathological situations, excess radicals can accumulate, resulting in oxidative stress. Oxidative stress has been related to cardiovascular disease, cancer, and other chronic diseases that account for a major portion of deaths today. Antioxidants are compounds that hinder the oxidative processes and thereby delay or prevent oxidative stress. In this sense, magnesium is one of the physiological, efficient antioxidant. Magnesium plays a role in more than 300 enzymatic reactions and is critically involved in energy metabolism, glucose utilization, protein synthesis, fatty acid synthesis and breakdown, ATPase functions, and virtually all hormonal reactions. This article summarizes the process of oxidative stress and the pathways by which it relates to magnesium.
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PMID:[Oxidative stress and magnesium]. 1569 57


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