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Cytochrome C. (cytochrome + c)
Selected AbstractsForced cytochrome B gene mutation expression induces mitochondrial proliferation and prevents apoptosis in human uroepithelial SV-HUC-1 cells,,INTERNATIONAL JOURNAL OF CANCER, Issue 12 2009Santanu Dasgupta Abstract Mitochondria encoded Cytochrome B (CYTB) gene mutations were reported in tumors of different anatomic origin but the functional significance of these mutations are not well studied. Earlier, we found a 7-amino acid deletion mutation in the CYTB gene in a primary bladder cancer patient. In the present study, we overexpressed this 7-amino acid deletion mutation of CYTB gene in SV-40 transformed human uroepithelial HUC-1 cells. The nuclear transcribed mitochondrial CYTB (mtCYTB) was targeted into the mitochondria and generated increased copies of mitochondria and mitochondrial COX-I protein in the transfected HUC-1 cells. The proapoptotic protein Bax largely remained confined to the cytoplasm of the mtCYTB transfected HUC-1 cells without release of Cytochrome C. The downstream apoptotic proteins PARP also remained uncleaved along with increased Lamin B1 in the mtCYTB transfected cells. Our results demonstrate that forced overexpression of mtCYTB in transformed human uroepithelial HUC-1 cells triggered mitochondrial proliferation and induction of an antiapoptotic signaling cascade favoring sustained cellular growth. Coding mitochondrial DNA mutations appear to have significant functional contribution in tumor progression. Published 2009 UICC. [source] ,-Fetoprotein positively regulates cytochrome c -mediated caspase activation and apoptosome complex formationFEBS JOURNAL, Issue 21 2003Lidia Semenkova Previous results have shown that the oncoembryonic marker ,-fetoprotein (AFP) is able to induce apoptosis in tumor cells through activation of caspase 3, bypassing Fas-dependent and tumor necrosis factor receptor-dependent signaling. In this study we further investigate the molecular interactions involved in the AFP-mediated signaling of apoptosis. We show that AFP treatment of tumor cells is accompanied by cytosolic translocation of mitochondrial cytochrome c. In a cell-free system, AFP mediates processing and activation of caspases 3 and 9 by synergistic enhancement of the low-dose cytochrome c -mediated signals. AFP was unable to regulate activity of caspase 3 in cell extracts depleted of cytochrome c or caspase 9. Using high-resolution chromatography, we show that AFP positively regulates cytochrome c/dATP-mediated apoptosome complex formation, enhances recruitment of caspases and Apaf-1 into the complex, and stimulates release of the active caspases 3 and 9 from the apoptosome. By using a direct protein,protein interaction assay, we show that pure human AFP almost completely disrupts the association between processed caspases 3 and 9 and the cellular inhibitor of apoptosis protein (cIAP-2), demonstrating its release from the complex. Our data suggest that AFP may regulate cell death by displacing cIAP-2 from the apoptosome, resulting in promotion of caspase 3 activation and its release from the complex. [source] Bid-dependent generation of oxygen radicals promotes death receptor activation,induced apoptosis in murine hepatocytesHEPATOLOGY, Issue 2 2004Wen-Xing Ding Activation of tumor necrosis factor receptor 1 or Fas leads to the generation of reactive oxygen species, which are important to the cytotoxic effects of tumor necrosis factor , (TNF-,) or Fas ligand. However, how these radicals are generated following receptor ligation is not clear. Using primary hepatocytes, we found that TNF-, or anti,Fas antibody,induced burst of oxygen radicals was mainly derived from the mitochondria. We discovered that Bid,a pro-death Bcl-2 family protein activated by ligated death receptors,was the main intracellular molecule signaling the generation of the radicals by targeting to the mitochondria and that the majority of oxygen radical production was dependent on Bid. Reactive oxygen species contributed to cell death and caspase activation by promoting FLICE-inhibitory protein degradation and mitochondrial release of cytochrome c. For the latter part, the oxygen radicals did not affect Bak oligomerization but instead promoted mitochondrial cristae reorganization and membrane lipid peroxidation. Antioxidants could reverse these changes and therefore protect against TNF-, or anti,Fas-induced apoptosis. In conclusion, our studies established the signaling pathway from death receptor engagement to oxygen radical generation and determined the mechanism by which reactive oxygen species contributed to hepatocyte apoptosis following death receptor activation. (HEPATOLOGY 2004;40:403,413.) [source] Effect of amyloid ,-peptide on permeability transition pore: A comparative studyJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2002Paula I. Moreira Abstract A potentially central factor in neurodegeneration is the permeability transition pore (PTP). Because of the tissue-specific differences in pore properties, we directly compared isolated brain and liver mitochondria responses to the neurotoxic A, peptides. For this purpose, the following parameters were examined: mitochondrial membrane potential (,,m), respiration, swelling, ultrastructural morphology, and content of cytochrome c. Both peptides, A,25,35 (50 ,M) and A,1,40 (2 ,M), had a similar toxicity, exacerbating the effects of Ca2+, although, per se, they did not induce (PTP). In liver mitochondria, A, led to a drop in ,,m and potentiated matrix swelling and disruption induced by Ca2+. In contrast, brain mitochondria, exposed to the same conditions, demonstrated a higher capacity to accumulate Ca2+ before the ,,m drop and a slight increase of mitochondrial swelling compared with liver mitochondria. Furthermore, mitochondrial respiratory state 3 was depressed in the presence of A,, whereas state 4 was unaltered, resulting in an uncoupling of respiration. In both types of mitochondria, A, did not affect the content of cytochrome c. The ,,m drop was reversed when Ca2+ was removed by EGTA or when ADP plus oligomycin was present. Pretreatment with cyclosporin A or ADP plus oligomycin prevented the deleterious effects promoted by A, and/or Ca2+. It can be concluded that brain and liver mitochondria show a different susceptibility to the deleterious effect of A, peptide, brain mitochondria being more resistant to the potentiation by A, of Ca2+ -induced PTP. © 2002 Wiley-Liss, Inc. [source] Hyperstability and crystal structure of cytochrome c555 from hyperthermophilic Aquifex aeolicusACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2009Marii Obuchi In order to elucidate the relationship between the stability and the structure of the monohaem cytochrome c555 (AA c555) from the hyperthermophilic bacterium Aquifex aeolicus, chemical denaturation and crystal structure determination were carried out. AA c555 exhibited higher stability than the thermophilic Hydrogenobacter thermophilus cytochrome c552 (HT c552), which is one of the most stable cytochromes c. The three-dimensional crystal structure of AA c555, which was determined using the multiple anomalous dispersion technique at 1.15,Å resolution, included a unique 14-residue extra helix, while the side-chain interactions of several amino-acid residues responsible for the stability of HT c552 were conserved in AA c555. The side chain of the Met61 residue in the extra helix was aligned towards the haem, forming a coordination bond between the Met S and haem Fe atoms. In other cytochromes c the corresponding regions always form , loops which also include the haem-liganding Met residue and are known to be involved in the initial step in cytochrome c denaturation. The formation of the extra helix in AA c555 results in the highest helix content, 59.8%, among the monohaem cytochromes c. The extra helix should mainly contribute to the hyperstability of AA c555 and is presumed to be a novel strategy of cytochromes c for adaptation to a hyperthermophilic environment. [source] | |||||||||||||