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Apoptotic Signaling Pathways (apoptotic + signaling_pathway)
Selected AbstractsComparative proteomic analysis associated with term placental insufficiency in cloned pigPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2007So-Young Lee Abstract Somatic cell-derived nuclear transfer (scNT) is a method of animal cloning in which the oocyte reprograms a somatic cell nucleus to divide and execute developmental programs. Despite many successes in this field, cloning by scNT remains very inefficient. Unlike other cloned animals, pigs derived by scNT have placentas with severe villous hypoplasia. To obtain a better understanding of the protein networks involved in this phenomenon, we assessed global protein expression profiles in term placentas from scNT-derived and control animals. Proteomic analysis of term placentas from scNT-derived animals identified 43 proteins that were differentially expressed compared to control animals. Among them, 14-3-3 proteins and Annexin V, which are closely involved in the apoptotic signaling pathway, were significantly down- and up-regulated, respectively. Western blot analysis and immunohistochemistry indicated that down-regulation of 14-3-3 proteins in scNT-derived placentas induced apoptosis of cytotrophoblast cells via mitochondria-mediated apoptosis. Taken together, our results suggest that placental insufficiency in scNT-derived placentas may be due to apoptosis, induced in part by the down-regulation of 14-3-3 proteins and up-regulation of Annexin V. They also indicate that proteomic maps represent an important tool for future studies of placental insufficiency and pathology. [source] The initiator caspase, caspase-10,, and the BH-3-only molecule, Bid, demonstrate evolutionary conservation in Xenopus of their pro-apoptotic activities in the extrinsic and intrinsic pathwaysGENES TO CELLS, Issue 7 2006Katsuya Kominami Two major apoptotic signaling pathways have been defined in mammals, the extrinsic pathway, initiated by ligation of death receptors, and the intrinsic pathway, triggered by cytochrome c release from mitochondria. Here, we identified and characterized the Xenopus homologs of caspase-10 (xCaspase-10,), a novel initiator caspase, and Bid (xBid), a BH3-only molecule of the Bcl-2 family involved in both the extrinsic and intrinsic pathways. Exogenous expression of these molecules induced apoptosis of mammalian cells. By biochemical and cytological analyses, we clarified that xCaspase-10, and xBid exhibit structural and functional similarities to their mammalian orthologues. We also detected xCaspase-10, and xBid transcripts during embryogenesis by whole-mount in situ hybridization and RT-PCR analysis. Microinjection of mRNA encoding a protease-defect xCaspase-10, mutant into embryos resulted in irregular development. Enforced expression of active xBid induced cell death in developing embryos. Using transgenic frogs established to allow monitoring of caspase activation in vivo, we confirmed that this form of cell death is caspase-dependent apoptosis. Thus, we demonstrated that the machinery governing the extrinsic and intrinsic apoptotic pathways are already established in Xenopus embryos. Additionally, we propose that the functions of the initiator caspase and BH3-only molecule are evolutionarily conserved in vertebrates, functioning during embryonic development. [source] Thioredoxin system inhibitors as mediators of apoptosis for cancer therapyMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 1 2009Kathryn F. Tonissen Abstract The thioredoxin (Trx) system is a major antioxidant system integral to maintaining the intracellular redox state. It contains Trx, a redox active protein, which regulates the activity of various enzymes including those that function to counteract oxidative stress within the cell. Trx can also scavenge reactive oxygen species (ROS) and directly inhibits proapoptotic proteins such as apoptosis signal-regulating kinase 1 (ASK1). The oxidized form of Trx is reduced by thioredoxin reductase (TrxR). The cytoplasm and mitochondria contain equivalent Trx systems and inhibition of either system can lead to activation of apoptotic signaling pathways. There are a number of inhibitors with chemotherapy applications that target either Trx or TrxR to induce apoptosis in cancer cells. Suberoylanilide hydroxamic acid (SAHA) is effective against many cancer cells and functions by up-regulating an endogenous inhibitor of Trx. Other compounds target the selenocysteine-containing active site of TrxR. These include gold compounds, platinum compounds, arsenic trioxide, motexafin gadolinium, nitrous compounds, and various flavonoids. Inhibition of TrxR leads to an accumulation of oxidized Trx resulting in cellular conditions that promote apoptosis. In addition, some compounds also convert TrxR to a ROS generating enzyme. The role of Trx system inhibitors in cancer therapy is discussed in this review. [source] Intracellular death platform steps-in: Targeting prostate tumors via endoplasmic reticulum (ER) apoptosisTHE PROSTATE, Issue 15 2008Steven R. Schwarze Abstract Molecular targeting of apoptotic signaling pathways has been extensively studied in recent years and directed towards the development of effective therapeutic modalities for treating advanced androgen-independent prostate tumors. The majority of therapeutic agents act through intrinsic or mitochondrial pathways to induce programmed cell death. The induction of apoptosis through endoplasmic reticulum (ER) stress pathways may provide an alternative to treat patients. The functional interaction between the BCL-2 family members and regulation of calcium homeostasis in the ER provides a critical link to the life or death outcome of the cell. Apoptosis induction mediated by ER stress-inducing agents is just beginning to be exploited for therapeutic targeting of prostate tumors. Insightful dissection of recently discovered apoptotic signaling pathways that function through the endoplasmic reticulum may identify novel molecules that could effectively target both androgen-dependent and androgen-independent prostate tumors. In this review, we focus on linking ER stress-induced apoptosis to therapeutic targeting of prostate tumors and dissect its cross-talk with the intrinsic and extrinsic apoptotic pathways. Prostate 68: 1615,1623, 2008. © 2008 Wiley-Liss, Inc. [source] 3135: Modulation of apoptotic signaling pathways to promote survival of endothelial cells by gene therapyACTA OPHTHALMOLOGICA, Issue 2010T FUCHSLUGER Purpose Corneal transplantation is the most common transplantation worldwide. Surgeons and eye banks face major problems: (1) shortage of tissue in aging populations, (2) loss of high-quality tissue due to cell loss during storage, (3) graft failure. It has been demonstrated that EC loss is mediated by the cells' intrinsic death machinery resulting in apoptosis. Identification of survival strategies could raise the availability of tissue, with a significant impact on transplantation by lowering graft rejection rate. The purpose of this study different apoptotic pathways and to determine the protective effect of the anti-apoptotic proteins bcl-xL and p35. Methods Intrinsic (mitochondria-mediated) and extrinsic (ligand-mediated) apoptotic pathways were selectively activated to provoke apoptosis of murine and human corneal endothelial cells suspensions and corneas. Gene transfer of bcl-xL or p35 was accomplished, survival of EC was determined by flow cytometry and laser scanning microscopy. Results Interestingly, we were able to determine distinct differences in cell survival enhancement depending on the type of overexpressed protein. Whereas uninfected controls showed significant EC death, gene-therapeutically treated EC demonstrated significantly increased cell survival. We will present data on the efficacy of certain anti-apoptotic proteins in select pathways. Conclusion Exploring inhibitory strategies of EC death can lead to clinically relevant survival strategies with significant impact on corneal grafting. [source] | |||||||||||||