Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasminogen activator inhibitor type 1 (PAI-1) has been shown to be an independent risk factor for coronary artery disease, myocardial infarction, and cerebrovascular events. Previous studies on variations in plasma PAI-1 levels and associations between PAI-1 levels and PAI-1 genotypes have suggested that PAI-1 expression maybe regulated in a genotype-specific manner by insulin, hypertriglyceridemic very low-density lipoprotein, and lipoprotein. We investigated whether basal transcription of the PAI-1 gene also is regulated in a genotype-specific manner. Allele-specific polymerase chain reaction-amplified fragments containing a 4G/5G polymorphism of the PAI-1 gene promoter were ligated into the chloramphenicol acetyltransferase (CAT) reporter gene. The constructs of p4G-CAT or pSG-CAT and pSV-beta-galactosidase as an internal control were transiently cotransfected into human HepG2 hepatoma cells. Electrophoresis mobility shift assays (EMSA) employed a fragment from positions -687 to -664 (4G allele) or from -688 to -664 (5G allele) labeled with adenosine triphosphate tagged with phosphorous 32 in the gamma position and used nuclear extracts of HepG2 cells. Analysis of CAT produced by constructs containing the PAI-1 4G or 5G allele showed similar 3-fold increases in CAT activity in the PAI-1 4G/4G and PAI-1 5G/5G constructs, compared with the CAT activity in the pCAT3-Basic construct. Analyses using the probes containing the 4G or 5G allele site in the EMSA assay revealed no difference in the binding of nuclear protein. Our in vitro assay of basal transcription suggests no difference in the transcriptional activities of the alleles of the PAI-1 4G/5G polymorphism.
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PMID:No association of the plasminogen activator inhibitor-1 promoter 4G/5G polymorphism with inhibitor level during basal transcription in vitro. 1521 74

Gene therapy is emerging as a realistic addition to the therapeutic arsenal in heart failure, but the search for suitable vectors for cardiac transfection is still ongoing. In this study, we explore the applicability of recombinant Semliki Forest virus (SFV) in heart failure. SFV was intracoronarily delivered 2 weeks after induction of myocardial infarction in the rat model for heart failure. Duration of SFV expression was determined, and tissue distribution was studied by histochemical, biochemical, and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Expression of SFV-mediated transfection in the heart reached its maximum after 48-72 h and subsided within a week. Intracoronary administration of SFV efficiently transfected the non-infarcted cardiac wall, resulting in high levels of beta-galactosidase (beta-gal) activity (1337 +/- 537 IU/mg) and lacZ RNA in the hearts of all rats, whereas brain, kidney, liver, lung, spleen, and testis were lacZ negative. In conclusion, intracoronarily delivered SFV has a favourable distribution pattern, showing expression of the transgene restricted to the heart.
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PMID:Semliki Forest virus is an efficient and selective vector for gene delivery in infarcted rat heart. 1524 44

We have tested the feasibility of using recombinant adeno-associated virus (rAAV) vectors as a tool for labeling bone marrow (BM) cells in vivo. We infected BM cells of donor FVB mice with rAAV vectors containing the lacZ gene for 2 h. We then injected the rAAV-infected cells to lethally irradiated-recipient FVB mice. Peripheral blood (PB), BM and spleen harvested at 4 weeks after BM transplant (BMT) demonstrated stable engraftment in beta-galactosidase (beta-gal) expression. In contrast, Dil-labeling displayed only a faint signal 4 weeks after BMT. To analyze the kinetics of BM cells, we injected vascular endothelial growth factor (VEGF), which promotes mobilization of BM cells. Administration of VEGF protein significantly increased the rAAV-mediated beta-gal expression in PB and BM of recipient mice. Moreover, when myocardial infarction was induced in BMT mice, the ischemic area exhibited significant beta-gal staining in rAAV-labeled BMT group. rAAV vectors programmed stable transduction in BM cells in vivo through rapid infection. rAAV appears to represent a useful vector for labeling BM cells ex vivo prior to BMT for analysis of cardiovascular therapeutic purposes.
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PMID:Use of recombinant adeno-associated viral vectors as a tool for labeling bone marrow cells. 1585 May 73

Reduced nitric oxide (NO) in the brain might contribute to enhanced sympathetic drive in heart failure (HF). The aim of this study was to determine whether increased NO production induced by local overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarius (NTS) of the brain stem reduces the enhanced sympathetic drive in mice with HF. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. MI mice exhibited left ventricular dilatation and a reduced left ventricular ejection fraction. Urinary norepinephrine excretion in MI mice was greater than that in sham-operated mice, indicating that sympathetic drive was enhanced in this model. Thus this model has features that are typical of HF. Western blot analysis and immunohistochemical staining for neuronal NOS (nNOS) indicated that nNOS protein expression was significantly reduced in the brain stem of MI mice. MI mice had a significantly smaller increase in blood pressure evoked by intracisternal injection of N(G)-monomethyl-L-arginine than sham-operated mice. Adenoviral vectors encoding either eNOS (AdeNOS) or beta-galactosidase (Adbeta gal) were transfected into the NTS to examine the effect of increased NO production in the NTS on the enhanced sympathetic drive in HF. After the gene transfer, urinary norepinephrine excretion was reduced in AdeNOS-transfected MI mice but not in Adbeta gal-transfected MI mice. These results indicate that nNOS expression in the brain stem, especially in the NTS, is reduced in the MI mouse model of HF, and increased NO production induced by overexpression of eNOS in the NTS attenuates the enhanced sympathetic drive in this model.
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PMID:Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction. 1600 46

Animal and early clinical studies have provided evidence suggesting that intracoronary administration of autologous bone marrow-derived cells results in improved outcome following myocardial infarction. Animal studies with cultured marrow stromal cells (MSC) have provided similar data. Cells with properties that are similar to MSC have been identified in adipose tissue. Other groups have demonstrated in vivo differentiation of adipose tissue-derived cells (ADC) into cells exhibiting biochemical and functional markers of cardiac myocytes, including spontaneous beating. Based on these observations, the objective of the present study was to determine whether ADC might undergo similar differentiation in vivo in the context of myocardial injury.ADC were isolated from subcutaneous adipose tissue of Rosa26 mice (which express the beta-galactosidase transgene in almost every tissue) and injected into the intraventricular chamber of B6129S recipient mice immediately following induction of myocardial cryoinjury. Groups of recipients were euthanized at 24 hours, 7 and 14 days post surgery and examined for the presence of donor-derived cells within the heart.Beta-gal positive cells were identified in the infarcts of ADC-treated animals. No staining was observed in uninjured myocardium or in infarcts of control animals. Immunohistochemical analysis revealed co-expression of beta-gal with Myosin Heavy Chain, Nkx2.5 and with Troponin I. Co-expression of beta-galactosidase with Connexin 43, CD31, von Willebrand factor, MyoD or CD45 was not detected.Thus, these data indicate that adipose tissue contains a population of cells that has the ability to engraft injured myocardium and that this engraftment is associated with expression of cardiomyocytic markers by donor-derived cells.
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PMID:Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury. 1608 55

Initial studies have suggested that transplantation of embryonic stem (ES) cells following myocardial infarction (MI) in animal models is beneficial; however, the mechanism of benefit is largely unknown. The present study investigated the fate of mouse ES cells transplanted post-MI to determine if the ES cells give rise to the range of major cell types present in the native myocardium. MI was produced by coronary artery ligation in C57BL/6 mice. Two different mouse ES cell lines, expressing eGFP and beta-galactosidase, respectively, were tested. Post-MI intramyocardial injection of 3 x 10(4) ES cells was compared to injection of media alone. Histochemistry and immunofluorescence were used to track the transplanted ES cells and identify the resulting cell types. Echocardiography assessed the cardiac size and function in a blinded fashion. Two weeks post-MI, engraftment of the transplanted ES cells was demonstrated by eGFP or beta-galactosidase-positive cells in the infarct region without evidence for tumor formation. Co-immunolabeling demonstrated that the transplanted ES cells had become cardiomyocytes, vascular smooth muscle, and endothelial cells. Echocardiographic analysis showed that ES cell transplantation resulted in reduced post-MI remodeling of the heart and improved cardiac function. In conclusion, transplanted mouse ES cells can regenerate infarcted myocardium in part by becoming cardiomyocytes, vascular smooth muscle, and endothelial cells that result in an improvement in cardiac structure and function. Therefore, ES cells hold promise for myocardial cellular therapy.
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PMID:Transplantation of embryonic stem cells into the infarcted mouse heart: formation of multiple cell types. 1628 79

Myocardial remodeling after myocardial infarction (MI) is associated with increased levels of the matrix metalloproteinases (MMPs). Levels of two MMP species, MMP-2 and MMP-9, are increased after MI, and transgenic deletion of these MMPs attenuates post-MI left ventricular (LV) remodeling. This study characterized the spatiotemporal patterns of gene promoter induction for MMP-2 and MMP-9 after MI. MI was induced in transgenic mice in which the MMP-2 or MMP-9 promoter sequence was fused to the beta-galactosidase reporter, and reporter level was assayed up to 28 days after MI. Myocardial localization with respect to cellular sources of MMP-2 and MMP-9 promoter induction was examined. After MI, LV diameter increased by 70% (P < 0.05), consistent with LV remodeling. beta-Galactosidase staining in MMP-2 reporter mice was increased by 1 day after MI and increased further to 64 +/- 6% of LV epicardial area by 7 days after MI (P < 0.05). MMP-2 promoter activation occurred in fibroblasts and myofibroblasts in the MI region. In MMP-9 reporter mice, promoter induction was detected after 3 days and peaked at 7 days after MI (53 +/- 6%, P < 0.05) and was colocalized with inflammatory cells at the peri-infarct region. Although MMP-2 promoter activation was similarly distributed in the MI and border regions, activation of the MMP-9 promoter was highest at the border between the MI and remote regions. These unique findings visually demonstrated that activation of the MMP-2 and MMP-9 gene promoters occurs in a distinct spatial relation with reference to the MI region and changes in a characteristic time-dependent manner after MI.
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PMID:Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction. 1676 34

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

We have previously shown that mouse embryonic stem (ES) cells transplanted following myocardial infarction (MI) differentiate into the major cell types in the heart and improve cardiac function. However, the extent of regeneration was relatively meager compared with the observed functional improvement. Therefore, we hypothesize that mechanisms in addition to regeneration contribute to the functional improvement from ES cell therapy. In this study, we examined the effect of mouse ES cells transplanted post-MI on cardiac apoptosis, fibrosis, and hypertrophy. MI was produced by left coronary artery ligation in C57BL/6 mice. Two different mouse ES cell lines, expressing enhanced green fluorescent protein and beta-galactosidase, respectively, were tested. Post-MI intramyocardial injection of 3 x 10(4) ES cells was compared with injection of medium alone. Terminal deoxynucleotidyl nick end labeling (TUNEL), immunofluorescence, and histology were used to examine the effect of transplanted ES cells on apoptosis, fibrosis, and hypertrophy. Two weeks post-MI, ES cell-transplanted hearts exhibited a significant decrease in TUNEL-stained nuclei (mean +/- SE; MI+medium = 12 +/- 1.5%; MI+ES cells = 6.6 +/- 1%, P < 0.05). TUNEL-positive nuclei were confirmed to be apoptotic by colabeling with a caspase-3 antibody. Cardiac fibrosis was 57% less in the MI+ES cell group compared with the MI + medium group (P < 0.05) as shown with Masson's trichrome staining. Picrosirius red staining confirmed a decreased amount of collagen present in the MI+ES cell group. Cardiomyocyte hypertrophy was significantly decreased following ES cell transplantation compared with medium control animals. In conclusion, transplanted mouse ES cells in the infarcted heart inhibit apoptosis, fibrosis, and hypertrophy, thereby reducing adverse remodeling.
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PMID:Transplanted embryonic stem cells following mouse myocardial infarction inhibit apoptosis and cardiac remodeling. 1798 30

There is an association between obesity and heart failure associated with LV dysfunction. Adiponectin is an adipocyte-derived hormone that is downregulated in obesity. Here, we examined the role of adiponectin in cardiac remodeling after myocardial infarction with loss- and gain-of-function genetic manipulations in an experimental model. Myocardial infarction was created in adiponectin-deficient (APN-KO) and wild-type (WT) mice by the permanent ligation of the left anterior descending (LAD) artery. For some experiments, adenoviral vectors expressing adiponectin or beta-galactosidase were delivered systemically. Cardiac structure and function were assessed by echocardiographic and Millar catheter measurements. Myocardial capillary density was assessed by staining with anti-CD31 antibody. Myocyte apoptotic activity was determined by TUNEL-staining. Myocardial interstitial fibrosis was evaluated by Masson's trichrome staining. APN-KO mice showed exacerbated left ventricular (LV) dilation, myocyte hypertrophy and contractile dysfunction compared with WT mice at 4 weeks after LAD ligation. Impaired LV function in APN-KO mice was coupled to myocyte hypertrophy, increased apoptotic activity and interstitial fibrosis in the remote zone, and reduced capillary density in the infarct border zone. No difference in infarct size was observed between WT and APN-KO mice. Administration of adenovirus-mediated adiponectin in WT mice resulted in decreased LV dilatation and improved LV function that was associated with increased capillary density in the infarct border zone and decreased myocyte hypertrophy, diminished myocardial apoptosis and decreased interstitial fibrosis in the remote zone. These data suggest that adiponectin protects against the development of systolic dysfunction after myocardial infarction through its abilities to suppress cardiac hypertrophy and interstitial fibrosis, and protect against myocyte and capillary loss.
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PMID:Adiponectin protects against the development of systolic dysfunction following myocardial infarction. 1749 64


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