Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HIV-seropositive individuals are at an increased risk for an accelerated form of emphysema. The purpose of this study was to determine the distribution of HIV-1 RNA in lung tissues and correlate this with the histologic findings and expression of matrix metalloproteases (MMPs). Reverse transcriptase (RT) in situ PCR analysis was performed on 11 AIDS lung autopsy specimens which showed varying degrees of emphysematous changes. In each lung, HIV-1 RNA was detected. In areas of histologically normal lung, very rare HIV-1-infected cells were evident. In contrast, many HIV-1-infected cells were noted in areas of emphysema. HIV-1 gag RNA was evident primarily in macrophages; infected pneumocytes were also seen. Similarly, MMP mRNA and protein, primarily MMP-9, localized to the areas of emphysema. Colabeling experiments documented that MMP expression was found primarily in cells that were HIV-1 negative and adjacent to HIV-1-infected macrophages. These results suggest that AIDS-related emphysema may be due, in part, to direct infection by HIV-1 of, primarily, alveolar macrophages, and concomitant up-regulation of MMP expression in the neighboring, noninfected cells.
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PMID:Correlation of HIV-1 detection and histology in AIDS-associated emphysema. 1571 64

Exposure to environmental tobacco smoke has been epidemiologically linked to heart disease among nonsmokers. However, the molecular mechanism behind the pathogenesis of cardiac disease is unknown. In this study, we found that Wistar rats, exposed to tobacco cigarette smoke at doses of 5, 10, or 15 cigarettes for 30 min twice a day for 1 month, had a dose-dependently reduced heart weight to body weight ratio and enhanced interstitial fibrosis as identified by histopathologic analysis. The mRNA and activity of matrix metalloprotease-2 (MMP-2), representing the progress of cardiac remodeling, were also elevated in the heart. In addition, we used reverse-transcriptase polymerase chain reaction and Western blotting to demonstrate significantly increased levels of the apoptotic effecter caspase-3 in treated animal hearts. Dose-dependently elevated mRNA and protein levels of Fas, and promoted apoptotic initiator caspase-8 (active form), a molecule of a death-receptor-dependent pathway, coupled with unaltered or decreased levels of cytosolic cytochrome c and the apoptotic initiator caspase-9 (active form), molecules of mitochondria-dependent pathways, may be indicative of cardiac apoptosis, which is Fas death-receptor apoptotic-signaling dependent, but not mitochondria pathway dependent in rats exposed to second-hand smoke (SHS). With regard to the regulation of survival pathway, using dot blotting, we found cardiac insulin-like growth factor-1 (IGF-1) and IGF-1 receptor mRNA levels to be significantly increased, indicating that compensative effects of IGF-1 survival signaling could occur. In conclusion, we found that the effects of SHS on cardiomyocyte are mediated by the Fas death-receptor-dependent apoptotic pathway and might be related to the epidemiologic incidence of cardiac disease of SHS-exposed nonsmokers.
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PMID:Second-hand smoke-induced cardiac fibrosis is related to the Fas death receptor apoptotic pathway without mitochondria-dependent pathway involvement in rats. 1620 45

A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A(165) and VEGF-A(121)). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression.
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PMID:Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC). 1649 31