Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein (apo) E plays an important role in lipid metabolism, and the major isoforms of apoE (apoE2, apoE3, and apoE4) have significantly different metabolic effects. Apolipoprotein E4 is associated with a higher risk of both heart disease and Alzheimer's disease (AD). Patients homozygous for apolipoprotein E2 are predisposed to type III hyperlipoproteinemia, and apoE2 may be protective against AD. Structure/function studies have proved to be a useful tool in understanding how the different apoE isoforms result in different pathological consequences. As these studies continue, it is essential to have a reliable method to produce large quantities of apoE and mutants of apoE. We describe here a method of apoE production in Escherichia coli strain BL21(DE3). The cDNA from apoE isoforms was inserted into a pET32a vector with a T7 promoter and a fusion partner (thioredoxin). The T7 promoter results in high expression of an easily purified His-tagged fusion protein. A thrombin recognition site was positioned in the expression vector so that only two novel amino acids (Gly-Ser) are added to the amino terminus of apoE following the removal of thioredoxin. Approximately 20 mg of apoE is obtained from a 1-liter culture. The major isoforms of apoE produced with this system were extensively characterized for their ability to bind the low-density lipoprotein (LDL) receptor, for their characteristic lipid association preferences, and for their stability as measured by guanidine denaturation. The recombinant proteins behaved identically to plasma-derived apoE isoforms.
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PMID:Functional characterization of apolipoprotein E isoforms overexpressed in Escherichia coli. 1041 18

An increase in oxidative stress is thought to be involved in the progression of heart disease, but the serum level of thioredoxin (TRX), which regulates the cellular redox state, has not been investigated in patients with heart diseases. The present study determined serum TRX levels with a sandwich enzyme-linked immunosorbent assay in a total of 39 patients with dilated cardiomyopathy (DCM) (n=5), acute coronary syndrome (ACS) (n=7) or stable angina (n=18), including effort angina (n=7) and vasospastic angina (n=11), and in control subjects (n=7). The serum TRX level in patients with New York Heart Association (NYHA) functional classes III and IV (n=8, 33.3+/-8.6 ng/ml) was significantly higher than in the control subjects (n=7, 14.0+/-4.6 ng/ml). In addition, the serum TRX levels correlated positively with the severity of NYHA class, and negatively with the left ventricular ejection fraction. The serum TRX levels were elevated in patients with ACS and DCM compared with the controls. These results indicate a possible association between TRX concentration and the severity of heart failure.
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PMID:Serum thioredoxin (TRX) levels in patients with heart failure. 1140 28

Parasitic diseases such as sleeping sickness, Chagas' heart disease, and malaria are major health problems in poverty-stricken areas. Antiparasitic drugs that are not only active but also affordable and readily available are urgently required. One approach to finding new drugs and rediscovering old ones is based on enzyme inhibitors that paralyze antioxidant systems in the pathogens. These antioxidant ensembles are essential to the parasites as they are attacked in the human host by strong oxidants such as peroxynitrite, hypochlorite, and H2O2. The pathogen-protecting system consists of some 20 thiol and dithiol proteins, which buffer the intraparasitic redox milieu at a potential of -250 mV. In trypanosomes and leishmania the network is centered around the unique dithiol trypanothione (N1,N8-bis(glutathionyl)spermidine). In contrast, malaria parasites have a more conservative dual antioxidative system based on glutathione and thioredoxin. Inhibitors of antioxidant enzymes such as trypanothione reductase are, indeed, parasiticidal but they can also delay or prevent resistance against a number of other antiparasitic drugs.
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PMID:Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. 1565 67

The thioredoxin system helps maintain a reducing environment in cells, but thioredoxin functions as more than simply an antioxidant. Thioredoxin functions depend on the protein's redox state, as determined by two conserved cysteines. Key biologic activities of thioredoxin include antioxidant, growth control, and antiapoptotic properties, resulting from interaction with target molecules including transcription factors. Mechanisms by which thioredoxin regulates cell growth include binding to signaling molecules such as apoptosis signal-regulating kinase-1 (ASK-1) and thioredoxin-interacting protein (Txnip). The molecular interplay between thioredoxin, ASK-1, and Txnip potentially influences cell growth and survival in diverse human diseases such as cancer, diabetes, and heart disease. In this review, we focus on the structure of thioredoxin and its functional regulation of cell growth through the interactions with signaling molecules.
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PMID:Role of thioredoxin in cell growth through interactions with signaling molecules. 1703 56

The redox status of the extracellular compartment has only just been elucidated as a mechanism controlling intracellular signal transduction and correlates with aging, diabetes, heart disease and lung fibrosis. In the present paper, we describe a mechanism by which oxidizing extracellular environments, as maintained by the cysteine/cystine (Cys/CySS) redox couple, induce mitochondria-derived ROS (reactive oxygen species) generation and cause the activation of Nrf2 (nuclear factor-erythroid 2-related factor 2), inducing an antioxidant response. NIH 3T3 cells were cultured in medium with extracellular Cys/CySS redox potentials (Eh), ranging from 0 to -150 mV. Cellular and mitochondrial ROS production significantly increased in cells incubated under more oxidizing extracellular conditions (0 and -46 mV). Trx2 (thioredoxin-2) is a mitochondrial-specific oxidoreductase and antioxidant and became oxidized in cells incubated at 0 or -46 mV. MEFs (mouse embryonic fibroblasts) from Trx2-overexpressing transgenic (Trx2 Tg) mice produced less intracellular ROS compared with WT (wild-type) MEFs at the more oxidizing extracellular conditions. Nrf2 activity was increased in WT MEFs at the 0 or -46 mV conditions, but was inhibited in Trx2 Tg MEFs under the same conditions. Furthermore, Nrf2-regulated gene expression was significantly increased in the WT MEFs, but not in the Trx2 Tg MEFs. These results show that the Cys/CySS redox status in the extracellular compartment regulates intracellular ROS generated primarily in the mitochondria, which play an important role in the activation of Nrf2 and up-regulation of antioxidant and detoxification systems.
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PMID:Extracellular redox status regulates Nrf2 activation through mitochondrial reactive oxygen species. 1977 93

The thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in the myocardium, and hampering the Txn system may compromise cell survival. Calcium (Ca) imbalance is associated with a variety of cardiomyopathies, and dysregulation of Ca2+ homeostasis is often considered a critical starting point for heart disease. However, the roles of Txn and the Txn system in maintaining Ca2+ homeostasis in cardiomyocytes have been infrequently reported. Here, we examined the expression of genes associated with Ca2+ channels using a model of Txn suppression in cardiomyocyte cultures (siRNA and Txn inhibitor) and report that Txn knockdown can cause Ca2+ overload in the myocardial cytoplasm and release of endoplasmic reticulum (ER) Ca2+, which induces ER stress. Our results showed that Txn knockdown could lead to cytosolic Ca2+ overload through upregulated gene expression of Ca2+ channel-related genes in the cytoplasmic and ER membranes. Furthermore, we find that excessive Ca2+ concentrations in the cytoplasm may increase myocardial contraction, and heat shock proteins may play a protective role throughout the process. Our present study reveals a novel model of regulation for low Txn expression in myocardial injury.
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PMID:Thioredoxin silencing-induced cardiac supercontraction occurs through endoplasmic reticulum stress and calcium overload in chicken. 3033 51

High glucose and high fat are important inducements for the development and progression of diabetic cardiopathy. Salvianolic acid B (SAB), which is the most abundant and bioactive compound in Danshen, attenuates oxidative stress-related disorders, such as cardiovascular diseases, cerebral ischemia, and diabetes. However, the effect of SAB on diabetic cardiopathy is not clear. The aim of study was to investigate the effect and the underlying molecular mechanisms of SAB on diabetic cardiopathy in vitro model. The human umbilical vein endothelial (HUVEC) cells were treated with high glucose (HG, 30 mM) or high fat (palmitic acid, PA, 0.75 mM) in the presence or absence of SAB (100, 200, and 400 mg/L) and incubated for 24 h. We found that HG or PA induced apoptosis of HUVEC cells, while treatment with SAB inhibited the apoptosis. We also found that SAB reversed HG- or PA-induced oxidative stress, apoptosis cell cytokines production, and expression of thioredoxin-interacting protein (TXNIP). Moreover, SAB increased HG- or PA-induced expression of Sirtuin 1 (Sirt1), a nicotinamide adenine dinucleotide- (NAD+-) dependent histone deacetylase. Exposure of HUVEC cells to Ex527 (Sirt1 inhibitor) suppressed the effect of SAB on acetyl-p53 and procaspase-3 expressions. In conclusion, the results suggested that SAB could attenuate HUVEC cells damage treated with HG or PA via Sirt1 and might be a potential therapy agent for the diabetic cardiopathy treatment.
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PMID:Salvianolic Acid B Attenuates Apoptosis of HUVEC Cells Treated with High Glucose or High Fat via Sirt1 Activation. 3111 74