Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac myocyte disarray is the pathological hallmark of hypertrophic cardiomyopathy (HCM), a disease of sarcomeric proteins. Mutations in the cardiac troponin T (cTnT), a major gene responsible for HCM, are associated with severe myocyte disarray. To study the pathogenesis of cardiac myocyte disarray, we expressed normal and mutant cTnT proteins in the myocardium of adult rabbits via direct intramyocardial injection of recombinant adenoviruses. Aliquots of 1010 plaque-forming units of normal (Ad/CMV/cTnT-Arg92) and mutant (Ad/CMV/cTnT-Gln92) recombinant viruses or a control vector (Ad/DeltaE) virus were mixed with equal aliquots of a reporter virus (Ad/CMV/Lac-Z) and co-injected into the myocardium of adult rabbits (n = 12). One week following gene transfer, thin myocardial sections were obtained and analyzed for beta-galactosidase, messenger RNA (mRNA) and protein expression, hematoxylin and eosin, Masson's trichrome, immunofluorescence staining, and electron microscopy. The efficiency of gene transfer varied from 2% to 60% of the cells in an area approximately 2.5 mm in length. Northern blotting confirmed expression of the transgenes into mRNA. Immunoblotting of the myofibrillar protein extracts and indirect immunofluorescence staining confirmed expression and incorporation of the transgene proteins into myofibrils. Expression of the mutant cTnT was up to 18% of the endogenous. Light and electron microscopic studies showed normal cardiac myocyte and sarcomere structures. Thus, despite incorporation of the mutant cTnT-Gln92, stable myofibrillar formation and sarcomere assembly proceeded in vivo. The absence of myocyte and sarcomere disarray may reflect the duration, or the level of expression, or the extent of myofibrillar incorporation of the mutant cTnT-Gln92, as well as the site and timing of expression of the transgenes, and interspecies variation in the pathogenesis of HCM.
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PMID:In vivo short-term expression of a hypertrophic cardiomyopathy mutation in adult rabbit myocardium: myofibrillar incorporation without early disarray. 989 56

Recent evidence suggests that adult-derived stem cells, like their embryonic counterparts, are pluripotent. These simple, undifferentiated and uncommitted cells are able to respond to signals from their host tissue microenvironment and differentiate, producing progeny that display a phenotype characteristic of the mature cells of that tissue. We used a clonal stem cell line (termed WB-F344) that was derived from an adult male rat liver to investigate the possibility that uncommitted stem cells from a nonmyogenic tissue source would respond to the tissue microenvironment of the heart in vivo and differentiate into cardiac myocytes. Male WB-F344 cells that carry the Escherichia coli beta-galactosidase gene were identified in the left ventricular myocardium of adult female nude mice 6 weeks after transplantation. We confirmed the presence of a rat Y-chromosome-specific repetitive DNA sequence exclusively in the beta-galactosidase-positive myocytes by polymerase chain reaction and fluorescence in situ hybridization. Immunohistochemistry, using a cardiac troponin T-specific monoclonal antibody, and ultrastructural analysis confirmed a cardiac myocyte phenotype of the stem cell-derived myocytes. The beta-galactosidase-positive myocytes ranged from < 20 microm to 110 microm in length. The longer of these cells contained well-organized sarcomeres and myofibrils, and formed intercalated disks and gap junctions with endogenous (host-derived) myocytes, suggesting that WB-F344-derived myocytes participate in the function of the cardiac syncytium. These results demonstrate that adult liver-derived stem cells respond to the tissue microenvironment of the adult heart in vivo and differentiate into mature cardiac myocytes.
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PMID:Adult-derived stem cells from the liver become myocytes in the heart in vivo. 1139 67

Diets rich in natural antioxidants are associated with reduced risk of heart diseases. This study was aimed to evaluate the preventive role of naringin on cardiac troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker enzymes, electrocardiographic (ECG)-patterns and lysosomal enzymes in isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats subcutaneously injected with ISO (85mg/kg) at an interval of 24h for 2 days showed a significant increase in the levels of cTnT, intensity of the bands of LDH-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such as creatine kinase-MB (CK-MB), creatine kinase (CK), LDH, aspartate transaminase (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the activities of CK, LDH, AST and ALT in the heart and alterations in ECG-patterns. The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin-B and cathepsin-D) were increased significantly in serum and the heart of ISO-induced rats, but the activities of beta-glucuronidase and cathepsin-D were decreased significantly in the lysosomal fraction of the heart. Pretreatment with naringin (10, 20 or 40mg/kg) daily for a period of 56 days positively altered the levels of cTnT, intensity of the bands of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, ECG-patterns and lysosomal hydrolases in ISO-induced rats. Thus, naringin possess cardioprotective effect in ISO-induced MI in rats.
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PMID:Preventive effect of naringin on cardiac markers, electrocardiographic patterns and lysosomal hydrolases in normal and isoproterenol-induced myocardial infarction in Wistar rats. 1718 15

Adult-derived stem cells have recently been found to respond in vivo to inductive signals from the microenvironment and to differentiate into a phenotype that is characteristic of cells in that microenvironment. We examined the differentiation potential of an adult liver stem cell line (WBF344) in a cardiac microenvironment in vitro. WBF344 cells were established from a single cloned non-parenchymal epithelial cell isolated from a normal male adult rat liver. Genetically modified, WBF344 cells that express beta-galactosidase, green fluorescent protein (GFP) or mitochondrial red fluorescent protein (DsRed) were co-cultured with rat neonatal cardiac cells. After 4-14 days, we identified WBF344-derived cardiomyocytes that were elongated, binucleated and expressed the cardiac specific proteins cardiac troponin T, cardiac troponin I and N cadherin. These WBF344-derived cardiomyocytes also exhibited myofibrils, sarcomeres, and a nascent sarcoplasmic reticulum. Furthermore, rhythmically beating WBF344-derived cardiomyocytes displayed "cardiac-like" calcium transients similar to the surrounding neonatal cardiomyocytes. Fluorescent recovery after photobleaching demonstrated that WBF344-derived cardiomyocytes were electrically coupled with adjacent neonatal cardiomyocytes through gap junctions (GJs). Collectively, these results support the conclusion that these adult-derived liver stem cells respond to signals generated in a cardiac microenvironment in vitro acquiring a cardiomyocyte phenotype and function. The identification of micro-environmental signals that appear to cross germ layer and species specificities should prove valuable in understanding the regulation of normal development and stem cell differentiation in vivo.
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PMID:Acquired cell-to-cell coupling and "cardiac-like" calcium oscillations in adult stem cells in a cardiomyocyte microenvironment. 1794 43