Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proline oxidase (POX), localized on inner mitochondrial membranes, is encoded by a p53-induced gene and metabolically participates in p53-induced apoptosis. Previously, we showed that POX catalyzed the generation of reactive oxygen species (ROS). We and others have demonstrated that overexpression of POX, independent of p53, causes apoptotic cell death in a variety of cancer cells. But a necessary role for ROS remains uncertain. Therefore, we asked whether superoxide dismutases (SOD) and catalase (CAT), important antioxidant enzymes, might interfere with the POX-dependent induction of apoptosis. In this study, we used DLD-1 colorectal cancer cells stably transfected with the POX gene under the control of a tetracycline-inducible promoter. When doxycycline was removed from the culture medium and the expression of POX was induced, apoptotic cell death was initiated. To examine the importance of the ROS-dependent component of the pathway, we infected DLD-1 POX cells with recombinant adenoviruses containing MnSOD, CuZnSOD, CAT or varying combinations of these adenoviruses followed by induced expression of POX. The expression of MnSOD inhibited POX-induced apoptosis, but others did not. Mechanistically, mitochondria-localized MnSOD dramatically reduced the release of cytochrome c to cytosol by POX. Compared with control cells, MnSOD-expressing DLD-1 POX cells generated a higher concentration of H2O2 owing to dismutation of superoxide radicals, which was elevated by POX. Thus, these data further suggest that the generation of superoxide radicals plays a crucial role in POX-induced apoptosis and the process is partially blocked by MnSOD.
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PMID:MnSOD inhibits proline oxidase-induced apoptosis in colorectal cancer cells. 1581 12

Proline oxidase (POX), a mitochondrial inner-membrane protein, catalyzes the rate-limiting oxidation of proline to pyrroline- 5-carboxylate (P5C). Previously we showed that overexpression of POX is associated with generation of reactive oxygen species (ROS) and apoptosis in POX-inducible colorectal cancer cells, DLD-1.POX. We also showed expression of mitochondrial MnSOD partially blunts POX-induced ROS generation and apoptosis. To further investigate the molecular basis of POX-induced apoptosis, we utilized the DLD-1.POX cells to show that cells overproducing POX exhibit an L-proline-dependent apoptotic response. The apoptotic effect is specific for L-proline, detectable at 0.2 mM, maximal at 1 mM, and occurs during 48-72 h following the addition of L-proline to cells with maximally induced POX. The apoptotic response is mitochondria-mediated with release of cytochrome c, activation of caspase-9, chromatin condensation/DNA fragmentation, and cell shrinkage. We conclude that in the presence of proline, high POX activity is sufficient to induce mitochondria-mediated apoptosis.
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PMID:Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis. 1687 62

The expression of P450 enzymes and antioxidative enzymes in tumour tissue can have a major impact on the responsiveness of tumours to cancer chemotherapeutic drugs, therefore such information may be very precious when experiments are designed. The compressive information, concerning the expression of drug metabolism enzymes or antioxidative enzymes is still lacking, therefore in this study the expression of CYP1A1, CYP1B1 and mitochondrial superoxide dismutase MnSOD (both mRNA and protein) in a panel of eight commonly used cancer cell lines, representing four tumour tissues was assayed. In the study two ovarian cancer cell lines A2780 and SKOV-3, two colorectal cancer LOVO and DLD-1, two breast cancer derived MCF-7 and MDA-MB-231 and two cervical cancer cell lines HeLa and C33A were employed. The relatively high expression of all assayed enzymes was shown in MDA-MB-231 breast cancer cells, lack of cancer cell specific CYP1B1 protein was discovered in LOVO colorectal cells. In order to test possible correlation between expression of CYP1A1, CYP1B1 and MnSOD and modulators of their activity, cytotoxicity of resveratrol and its promising hydroxylated analogue 3,3',4,4',5,5'-trans-hexahydroxystilbene against cell lines used in experiment was assayed. The relatively high correlation was found between IC50 values calculated for 3,3',4,4',5,5'-trans-hexahydroxystilbene and expression of MnSOD (r = 0.6562).
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PMID:Expression of CYP1A1, CYP1B1 and MnSOD in a panel of human cancer cell lines. 2387 31