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10.1038/srep14296 http://scihub22266oqcxt.onion/10.1038/srep14296 C4606568!4606568 !26469226     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26469226 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Sci+Rep 2015 ; 5 (ä): 14296 Nephropedia Template TP {{tp|p=26469226 |t=2015. Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1? in cancer cells |pdf=|usr=}}{{26469226 }} gab.com Text Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1 in cancer cells JO: Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=26469226 #FOAvip Hypoxia-inducible factor-1? (HIF-1?) is a transcription factor that triggers adaptive responses upon low oxygen conditions and plays a crucial role in cancer metabolism and therapy resistance. Tetrathiomolybdate (TM), a therapy option for copper overload disorder, has also been shown to be capable of limiting tumor angiogenesis, although its underlying mechanism remains unclear. Using ovarian and endometrial cancer cell lines, we observed that TM downregulates HIF-1? protein levels and HIF-transcriptional targets involved in tumor angiogenesis and glycolysis, but did not affect HIF-1? protein synthesis. TM-mediated HIF-1? downregulation was suppressed when HIF-prolyl hydroxylase activity was pharmacologically inhibited using deferoxamine or dimethyloxaloylglycine, and also when the oxygen-dependent degradation domains of HIF-1?, which are responsible for the interaction with HIF-prolyl hydroxylase, were deleted. These findings suggest that TM causes HIF-1? downregulation in a HIF-prolyl hydroxylase-dependent manner. Our studies showed that TM inhibits the activity of the copper-dependent mitochondrial complex IV and reduces mitochondrial respiration, thereby possibly increasing oxygen availability, which is crucial for HIF-prolyl hydroxylase activity. Pimonidazole staining also showed that TM elevates oxygen tension in hypoxic cells. Our studies provide mechanistic evidence for TM-mediated HIF-1? regulation and suggest its therapeutic potential as a method of blocking angiogenesis in ovarian and endometrial tumors. Twit Text FOAVip Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1 in cancer cells ????Sci Rep http://www.kidney.de/pget.php?&tw=1&pmid=26469226 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26469226 #FOAvip English Wikipedia <ref>{{Cite pmid|26469226 }}</ref> Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1? in cancer cells #MMPMID26469226 Kim KK ; Abelman S ; Yano N ; Ribeiro JR ; Singh RK ; Tipping M ; Moore RG Sci Rep 2015[Oct]; 5 (ä): 14296 PMID26469226 show ga Hypoxia-inducible factor-1? (HIF-1?) is a transcription factor that triggers adaptive responses upon low oxygen conditions and plays a crucial role in cancer metabolism and therapy resistance. Tetrathiomolybdate (TM), a therapy option for copper overload disorder, has also been shown to be capable of limiting tumor angiogenesis, although its underlying mechanism remains unclear. Using ovarian and endometrial cancer cell lines, we observed that TM downregulates HIF-1? protein levels and HIF-transcriptional targets involved in tumor angiogenesis and glycolysis, but did not affect HIF-1? protein synthesis. TM-mediated HIF-1? downregulation was suppressed when HIF-prolyl hydroxylase activity was pharmacologically inhibited using deferoxamine or dimethyloxaloylglycine, and also when the oxygen-dependent degradation domains of HIF-1?, which are responsible for the interaction with HIF-prolyl hydroxylase, were deleted. These findings suggest that TM causes HIF-1? downregulation in a HIF-prolyl hydroxylase-dependent manner. Our studies showed that TM inhibits the activity of the copper-dependent mitochondrial complex IV and reduces mitochondrial respiration, thereby possibly increasing oxygen availability, which is crucial for HIF-prolyl hydroxylase activity. Pimonidazole staining also showed that TM elevates oxygen tension in hypoxic cells. Our studies provide mechanistic evidence for TM-mediated HIF-1? regulation and suggest its therapeutic potential as a method of blocking angiogenesis in ovarian and endometrial tumors. |Cell Line, Tumor [MESH] |Cell Respiration/drug effects [MESH] |Electron Transport Complex IV/*antagonists & inhibitors/*metabolism [MESH] |Gene Expression Regulation, Neoplastic/drug effects [MESH] |Humans [MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism [MESH] |Molybdenum/*pharmacology [MESH] |Neoplasms/genetics/*metabolism [MESH] |Oxygen/metabolism [MESH] |Phosphatidylinositol 3-Kinases/metabolism [MESH] |Proteolysis/drug effects [MESH] |Proto-Oncogene Proteins c-akt/metabolism [MESH]Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degr(epmc).pdf DeepDyve Pubget Overpricing