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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinase (ERK) promotes cell proliferation or differentiation, whereas c-jun N terminal kinase (JNK) and p38 MAPK are thought to inhibit cell growth and induce apoptosis. The MAPK family may plays some role during kidney development, when large-scale proliferation and apoptosis have been observed to occur. Also, in this period, the renin-angiotensin system is markedly activated. We have demonstrated that angiotensin-converting enzyme inhibition in the developing rat kidney increases apoptosis and decreases cell proliferation, which may account for renal growth impairment. The aim of this study, therefore, was to examine the relationship between the MAPK family and renin-angiotensin system during neonatal renal development. Newborn rat pups were treated with enalapril (30 mg . kg(-1) . d(-1)) or normal saline for 7 d. Right kidneys of both groups were selected for immunohistochemical stains of MAPKs and activating transcription factor-2 (ATF-2), and left kidneys were selected for reverse transcriptase-PCR and immunoblot analysis of MAPKs, phospho-MAPKs, and ATF-2. To determine whether apoptosis is involved in the same tubules that highly expressed JNK and p38, we performed terminal deoxynucleotide transferase-mediated nick-end labeling stain for apoptotic cells and immunohistochemical stains for JNK-2, p38, and ATF-2 expression in the serial sections from the same kidney of the enalapril-treated group. In the enalapril-treated group, JNK-2, p38, phospho-JNK-2, phospho-p38, and ATF-2 protein expressions were significantly increased, and their immunoactivities were strongly detected in the proximal tubular epithelial cells in the cortex, compared with the control group. Especially JNK-2 and p38 expressions were highly activated and were spatially in accordance with the occurrence of apoptosis. ERK1/2 and phospho-ERK expressions were not changed by enalapril. These results suggest that the expressions of the MAPK family are modulated by angiotensin-converting enzyme inhibition in the developing kidney. JNK and p38 may be implicated to participate in angiotensin II-related intracellular signaling pathways of renal apoptosis in the developing kidney.
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PMID:Angiotensin-converting enzyme inhibition modulates mitogen-activated protein kinase family expressions in the neonatal rat kidney. 1553 46

Ionizing radiation has been reported to promote accelerated or premature senescence in both normal and tumour cell lines. The current studies were designed to characterize the accelerated senescence response to radiation in the breast tumour cell in terms of its dependence on functional p53 and its relationship to telomerase activity, telomere lengths, expression of human telomerase reverse transcriptase (hTERT, the catalytic subunit of telomerase) and human telomerase RNA (hTR, the RNA subunit of telomerase), as well as the induction of cytogenetic aberrations. Studies were performed in p53 wild-type MCF-7 cells, MCF-7/E6 cells with attenuated p53 function, MDA-MB231 cells with mutant p53 and MCF-7/hTERT cells with constitutive expression of hTERT. Telomerase activity was measured by the telomeric repeat amplification protocol (TRAP assay), telomere lengths by the terminal restriction fragment (TRF) assay, hTR and hTERT expression by reverse transcriptase-polymerase chain reaction (RT-PCR), senescence by beta-galactosidase staining, and apoptosis by TdT-mediated d-UTP-X nick-end labelling (TUNEL assay). Widespread and extensive expression of beta-galactosidase, a marker of cellular senescence, was evident in MCF-7 breast tumour cells following exposure to 10 Gy of ionizing radiation. Radiation did not suppress expression of either hTERT or hTR, alter telomerase activity or induce telomere shortening. Senescence arrest was also observed in irradiated MCF-7/hTERT cells, which have elongated telomeres due to the ectopic expression of the catalytic component of telomerase. In contrast to MCF-7 cells, irradiated MDA-MB231 breast tumour cells and MCF-7/E6 cells failed to senesce and instead demonstrated a delayed apoptotic cell death. Irradiation produced chromosome end associated abnormalities, including end-to-end fusions (an indicator of telomere dysfunction) in MCF-7 cells, MCF-7/hTERT cells, as well as in MCF-7/E6 cells. When cells were maintained in culture following irradiation, proliferative recovery was evident exclusively after senescence while the cell lines which responded to radiation by apoptosis continued to decline in cell number. Accelerated senescence in response to ionizing radiation is p53 dependent and associated with telomer dysfunction but is unrelated to changes in telomerase activity or telomere lengths, expression of hTERT and hTR. In the absence of functional p53, cells are unable to arrest for an extended period, resulting in apoptotic cell death while accelerated senescence in cells expressing p53 is succeeded by proliferative recovery.
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PMID:p53-Dependent accelerated senescence induced by ionizing radiation in breast tumour cells. 1630 15

We investigated the potential of the cytotoxic enterotoxin (Act) of Aeromonas hydrophila to bind to 1869 human and 4319 yeast proteins, using protein microarray technology. Act was capable of binding nine different human proteins, including the SNARE complex scaffolding protein synaptosomal-associated protein 23 (SNAP23), galectin-3, and guanylate kinase 1 (GUK-1). Act was also able to bind to four of the yeast proteins examined, which included the vesicle tethering protein Vsp52. We verified interaction of Act with murine and human SNAP23, galectin-3, and GUK-1 by sandwich Western blot analysis. In order to determine the physiological relevance of Act binding to these three proteins, we performed small interfering RNA (siRNA) gene knockdown experiments in RAW 264.7 cells, a murine macrophage cell line in which Act-induced signaling and cell death is well characterized. Based on real-time reverse transcriptase-polymerase chain reaction, siRNA transfection of RAW 264.7 cells with specific oligonucleotides reduced the expression of genes encoding SNAP23, galectin-3, and GUK-1 by 62, 63, and 99%, respectively. Knockdown of galectin-3 and SNAP23, but not GUK-1, significantly reduced Act-induced apoptosis of host cells, as determined by TUNEL (TdT-mediated dUTP nick end labeling) assay, lactate dehydrogenase release, Giemsa staining, and reduction in activation of caspase 3, compared to toxin-treated macrophages that were transfected with a random sequence control siRNA. We also performed these assays using a human intestinal epithelial cell line (HT-29) and observed a similar trend of galectin-3 and SNAP23 association with Act-induced apoptosis. This is the first report of putative protein binding partners for this toxin and potential mediators/regulators of Act-induced apoptosis.
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PMID:Potential involvement of galectin-3 and SNAP23 in Aeromonas hydrophila cytotoxic enterotoxin-induced host cell apoptosis. 1642 11

Trypanosoma evansi, the cause of the disease Surra in livestock, is the most widely geographically distributed pathogenic trypanosome occurring in Africa, South and Central America, and Asia, where it causes significant economic loss. Although many studies have described the histopathology induced in the organs of mice infected with T. evansi, few studies have been conducted on gene expression in these organs. Here we used complementary DNA microarray to analyze the gene expression profiles in the liver and spleen of mice infected with T. evansi (STIB 806) at the peak parasitemia (7 days after infection). A total of 14,000 sequences including full length and partial complementary DNAs representing novel, known, and control genes of mouse were analyzed. Results from GeneOntology annotation showed that 158 genes in the liver and 73 genes in the spleen were up-regulated in the infected mice and that 178 genes in the liver and 117 genes in the spleen of infected mice were down-regulated compared with control (non-infected) mice. Most of these genes are metabolism, transport, protein biosynthesis, transcription factors, and nucleic acid binding protein-related genes. The changes of some important genes, such as heat shock protein 70 and proliferating cell nuclear antigen, were confirmed by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. TdT-mediated dUTP-digoxigenin nick end labeling analysis results revealed that extensive apoptosis occurred in the liver of infected mice at the peak of parasitemia. Our results provide a comprehensive profile of changes in gene expression in the liver and spleen of mice infected with T. evansi and may be helpful in understanding the pathogenesis of Surra at a molecular level.
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PMID:Analysis of gene expression profiles in the liver and spleen of mice infected with Trypanosoma evansi by using a cDNA microarray. 1884 6

The most characteristic change in psoriasis is markedly increased, persistent keratinocyte proliferation. The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. Cellular FLIP (cFLIP) is a close homologue of caspase 8 without the caspase activity that inhibits Fas signaling. The cFLIP protein is often expressed in human tumors and is believed to suppress antitumor immune responses involving the Fas system. PCNA is an auxiliary protein of DNA polymerase-5, which appears early in G1 and becomes more abundant in the S phase, thereafter declining during G2/M phases of the cell cycle. Thus, the PCNA staining profiles were used as markers of keratinocyte proliferation. Our objective was to obtain insight into the role of c-FLIP in kerarinocyte proliferation and to investigate further the pathogenesis of psoriasis. Using real time quantitative reverse transcriptase-polymerase chain reactions (RT-PCR) and immunohistochemical staining, we studied the expression of c-FLIP mRNA and protein in skin biopsies from psoriatic patients and healthy subjects. Apoptotic cells were evaluated using the terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. c-FLIP mRNA and protein expressions were significantly greater in lesional psoriatic epidermis compared with normal and non-lesional psoriatic epidermis (P < 0.01). c-FLIP was strongly expressed within all epidermal layers in lesional psoriatic skin, whereas weak c-FLIP staining was restricted to the basal and suprabasal layers in normal and non-lesional psoriatic epidermis. c-FLIP protein levels significantly correlated with PASI score, PCNA and apoptosis index (Spearman's rho = 0.83; rho = 0.61; rho = - 0.41; P < 0.05, respectively). We conclude that over-expression of c-FLIP in lesional psoriatic skin might contribute to abnormal keratinocyte proliferation due to a functional decrease in the apoptotic pathway.
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PMID:Expression of antiapoptotic protein c-FLIP is upregulated in psoriasis epidermis. 1905 32

Endothelin systems are believed to play important roles in the emergence and maintenance of functions of various organs during perinatal development, including the kidney. The present study was designed to investigate the roles of endothelin systems on physiologic renal growth and development. Newborn rat pups were treated with either Bristol-Myers Squibb-182874 (30 mg/kg/day), a selective endothelin A receptor (ET(A)R) antagonist, or vehicle for 7 days. To identify cellular changes, kidneys were examined for apoptotic cells by terminal deoxynucleotide transferase-mediated nick-end labeling stain and proliferating cell nuclear antigen (PCNA) by immunohistochemical (IHC) stain. To clarify the molecular control of these processes, immunoblots and reverse transcriptase-polymerase chain reaction for Clusterin, Bcl-2, Bcl-X(L), Bax, and p53 were performed. ETAR antagonist treatment resulted in reduced kidney weights, decreased PCNA-positive proliferating cells, and increased apoptotic cells. The protein expressions of renal Bcl-X(L) and Bax in the ETAR antagonist-treated group were significantly decreased, whereas the mRNA expressions of these genes were not changed. There were no significant differences in the expressions of Clusterin, Bcl-2, and p53. In conclusion, inhibition of endogenous endothelins impairs renal growth, in which decreased cellular proliferation, increased apoptosis and decreased expressions of renal Bcl-X(L) and Bax are possibly implicated.
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PMID:Endothelin A receptor blockade influences apoptosis and cellular proliferation in the developing rat kidney. 1927 Aug 27

Nonylphenol (NP) is the final biodegradation product of nonylphenol polyethoxylates, which are widely used surfactants in domestic and industrial products. Nonylphenol has been reported to have estrogenic activity and shown to have potential reproductive toxicity. However, its influence on immune system function remains unclear. In this study, we investigated the effects of nonylphenol on apoptosis and Fas/FasL gene expression in rat thymus. Nonylphenol were given orally by gavages at 125, 250, and 375mg/kg per day. Negative and positive controls were treated with the vehicle and E(2) 10ng/kg per day, respectively. Atrophy of thymus was determined by in situ morphological examination using hematoxylin and eosin staining. Apoptotic cells were identified by terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labeling (TUNEL) assay. A semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method was used to analyze Fas and FasL mRNA levels. The results showed that both nonylphenol and E(2) increased the rates of apoptotic death; reduced the expression of Fas; enhanced the expression of FasL. These findings demonstrated that nonylphenol with estrogen-like activity might affect the regulation of the immune function through thymocyte apoptosis. This apoptosis was mediated by altering the expression of Fas and FasL mRNA.
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PMID:Nonylphenol induces thymocyte apoptosis through Fas/FasL pathway by mimicking estrogen in vivo. 2178 9

Aflatoxin B1 (AFB1) and the hepatitis B virus X antigen (HBx) are linked to the formation of liver diseases and hepatocellular carcinoma (HCC). The aim of this study was to investigate the synergistic effects between HBx and AFB1 in causing liver disorders using a transgenic zebrafish animal model. Histopathology, Periodic acid-Schiff (PAS) staining, Sirius red staining, TdT-mediated dUTP Nick End Labeling (TUNEL) assay, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) were used to examine the livers of the HBx transgenic fish injected with AFB1. We found that HBx and AFB1 synergistically promoted steatosis as indicated by histopathological examinations and the increased expression of lipogenic factors, enzymes, and genes related to lipid metabolism. Moreover, treatment of AFB1 in HBx transgenic fish accelerated the development of liver hyperplasia and enhanced the expression of cell cycle related genes. PCNA was co-localized with active caspase 3 protein expression in HBx zebrafish liver samples and human HBV positive HCC samples by double fluorescence immunostaining. Finally, we found that in human patients with liver disease, significant glycogen accumulated in the inflammation, cirrhosis stage, and all cases of hepatocellular and cholangiocellular carcinoma showed a moderate cytoplasmic accumulation of glycogen. Our data demonstrated a synergistic effect of AFB1 and HBx on the regulation of lipid metabolism related genes and cell cycle/division-related genes which might contribute to enhanced steatosis and hyperplasia at 5.75months.
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PMID:Hepatitis B virus X antigen and aflatoxin B1 synergistically cause hepatitis, steatosis and liver hyperplasia in transgenic zebrafish. 2349 92

Cardiotoxicity is a well-recognized side effect induced by chemotherapeutic drugs such as anthracycline and trastuzumab through different mechanisms. Currently, accumulating evidence supports that dexrazoxane (DZR) can minimize the risk of cardiotoxicity. In this study, we investigated whether dexrzoxane could reduce cardiotoxicity in the treatment of anthracycline combined with trastuzumab. We randomly divided 90 experimental F344 rats into control group, chemotherapeutics and trastuzumab (doxorubicin [DOX] + herceptin [Her]) group, and chemotherapeutics, trastuzumab, and DZR (DOX + Her + DZR) group. Animal status and body weight, cardiac function, serum cardiac markers, cardiomyocyte apoptosis of the rats, and expression level of calpain-2 were evaluated. Left ventricular ejection fraction (LVEF) and fractional shortening (FS) of the left ventricle were observed. The serum levels of malondialdehyde (MDA) and cardiac troponin I (cTnI) and cardiomyocyte apoptosis were detected by enzyme linked immunosorbent assay and TdT-mediated dUTP nick end labeling assays. The mRNA and protein level of calpain-2 were measured by reverse transcriptase polymerase chain reaction and Western blot. We observed that the LVEF and FS of the left ventricle were significantly higher in the DOX + Her + DZR group than that in the DOX + Her group (P < 0.05). The serum levels of MDA and cTnI between DOX + Her group and DOX + Her + DZR group were significantly different. In addition, cardiomyocyte apoptosis in the DOX + Her + DZR group was significantly less severe than that in the DOX + Her group (P < 0.05). After DZR treatment, the calpain-2 mRNA and protein levels in the DOX + Her + DZR group were significantly higher than the DOX + Her group (P < 0.05). Our results suggest that DZR can effectively reduce the cardiotoxicity of combinatorial treatment of trastuzumab and anthracycline partly through upregulating calpain-2.
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PMID:Cardiac protective effects of dexrazoxane on animal cardiotoxicity model induced by anthracycline combined with trastuzumab is associated with upregulation of calpain-2. 2563 81


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