oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
The Involvement of Bax in Zinc-Induced Mitochondrial Apoptogenesis in Malignant Prostate Cells
Pei Feng, Tieluo Li, Zhixin Guan, Renty B Franklin, Leslie C Costello
Molecular Cancer , 2008, DOI: 10.1186/1476-4598-7-25
Abstract: The effects of zinc treatment on the Bax levels of PC-3 cells and on the mitochondria were determined. The exposure of isolated mitochondria to zinc results in an increase in membrane bound Bax, which is due to the mitochondrial insertion of endogenous resident Bax. The mitochondrial Bax/Bcl-2 ratio is increased by zinc treatment. Zinc treatment of PC-3 cells also increases the mitochondrial level of Bax. In addition, zinc treatment increases the cellular level of Bax and the cellular Bax/Bcl2 ratio. Down regulation of Bax in PC-3 cells eliminates the zinc induction of apoptosis. The increase in cellular Bax level appears to involve zinc induction of Bax gene expression.This report extends and confirms that physiological levels of zinc induce apoptosis in prostate cells. The study provides evidence that zinc is directly involved in facilitating a Bax-associated pore formation process that initiates mitochondrial apoptogenesis. This is enhanced by an additional effect of zinc on increasing the cellular level of Bax. To avoid the anti-tumor apoptogenic effects of zinc, the malignant cells in prostate cancer posses genetic/metabolic adaptations that prevent the cellular accumulation of zinc.An early event in the development and progression of prostate cancer is the metabolic transformation of normal zinc-accumulating epithelial cells to malignant cells that have lost the ability to accumulate zinc [for reviews see [1-3]]. This metabolic transformation is essential so that the tumor suppressive effects of zinc can be eliminated and the malignant process can proceed. One of the effects of zinc is the prevention of cell growth due to zinc-induced apoptosis that occurs in prostate cells. In previous studies [4-7], we reported that the uptake and accumulation of zinc results in the mitochondrial release of cytochrome c, which initiates the caspase cascade that leads to apoptosis. Moreover, the release of cytochrome c results from a direct and rapid interaction of cytosolic
A New View of the Lethal Apoptotic Pore  [PDF]
Gorka Basa?ez,Lucian Soane,J. Marie Hardwick
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001399
Abstract: Cell death by apoptosis is indispensable for proper development and tissue homeostasis in all multicellular organisms, and its deregulation plays a key role in cancer and many other diseases. A crucial event in apoptosis is the formation of protein-permeable pores in the outer mitochondrial membrane that release cytochrome c and other apoptosis-promoting factors into the cytosol. Research efforts over the past two decades have established that apoptotic pores require BCL-2 family proteins, with the proapoptotic BAX-type proteins being direct effectors of pore formation. Accumulating evidence indicates that other cellular components also cooperate with BCL-2 family members to regulate the apoptotic pore. Despite this knowledge, the molecular pathway leading to apoptotic pore formation at the outer mitochondrial membrane and the precise nature of this outer membrane pore remain enigmatic. In this issue of PLOS Biology, Kushnareva and colleagues describe a novel kinetic analysis of the dynamics of BAX-dependent apoptotic pore formation recapitulated in native mitochondrial outer membranes. Their study reveals the existence of a hitherto unknown outer mitochondrial membrane factor that is critical for BAX-mediated apoptotic pore formation, and challenges the currently popular view that the apoptotic pore is a purely proteinaceous multimeric assembly of BAX proteins. It also supports the notion that membrane remodeling events are implicated in the formation of a lipid-containing apoptotic pore.
A New View of the Lethal Apoptotic Pore  [PDF]
Gorka Basa?ez ,Lucian Soane,J. Marie Hardwick
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1001399
Abstract: Cell death by apoptosis is indispensable for proper development and tissue homeostasis in all multicellular organisms, and its deregulation plays a key role in cancer and many other diseases. A crucial event in apoptosis is the formation of protein-permeable pores in the outer mitochondrial membrane that release cytochrome c and other apoptosis-promoting factors into the cytosol. Research efforts over the past two decades have established that apoptotic pores require BCL-2 family proteins, with the proapoptotic BAX-type proteins being direct effectors of pore formation. Accumulating evidence indicates that other cellular components also cooperate with BCL-2 family members to regulate the apoptotic pore. Despite this knowledge, the molecular pathway leading to apoptotic pore formation at the outer mitochondrial membrane and the precise nature of this outer membrane pore remain enigmatic. In this issue of PLOS Biology, Kushnareva and colleagues describe a novel kinetic analysis of the dynamics of BAX-dependent apoptotic pore formation recapitulated in native mitochondrial outer membranes. Their study reveals the existence of a hitherto unknown outer mitochondrial membrane factor that is critical for BAX-mediated apoptotic pore formation, and challenges the currently popular view that the apoptotic pore is a purely proteinaceous multimeric assembly of BAX proteins. It also supports the notion that membrane remodeling events are implicated in the formation of a lipid-containing apoptotic pore.
Capsid Protein VP4 of Human Rhinovirus Induces Membrane Permeability by the Formation of a Size-Selective Multimeric Pore  [PDF]
Anusha Panjwani,Mike Strauss,Sarah Gold,Hannah Wenham,Terry Jackson,James J. Chou,David J. Rowlands,Nicola J. Stonehouse,James M. Hogle,Tobias J. Tuthill
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004294
Abstract: Non-enveloped viruses must deliver their viral genome across a cell membrane without the advantage of membrane fusion. The mechanisms used to achieve this remain poorly understood. Human rhinovirus, a frequent cause of the common cold, is a non-enveloped virus of the picornavirus family, which includes other significant pathogens such as poliovirus and foot-and-mouth disease virus. During picornavirus cell entry, the small myristoylated capsid protein VP4 is released from the virus, interacts with the cell membrane and is implicated in the delivery of the viral RNA genome into the cytoplasm to initiate replication. In this study, we have produced recombinant C-terminal histidine-tagged human rhinovirus VP4 and shown it can induce membrane permeability in liposome model membranes. Dextran size-exclusion studies, chemical crosslinking and electron microscopy demonstrated that VP4 forms a multimeric membrane pore, with a channel size consistent with transfer of the single-stranded RNA genome. The membrane permeability induced by recombinant VP4 was influenced by pH and was comparable to permeability induced by infectious virions. These findings present a molecular mechanism for the involvement of VP4 in cell entry and provide a model system which will facilitate exploration of VP4 as a novel antiviral target for the picornavirus family.
The Rubella Virus Capsid Is an Anti-Apoptotic Protein that Attenuates the Pore-Forming Ability of Bax  [PDF]
Carolina S. Ilkow,Ing Swie Goping,Tom C. Hobman
PLOS Pathogens , 2011, DOI: 10.1371/journal.ppat.1001291
Abstract: Apoptosis is an important mechanism by which virus-infected cells are eliminated from the host. Accordingly, many viruses have evolved strategies to prevent or delay apoptosis in order to provide a window of opportunity in which virus replication, assembly and egress can take place. Interfering with apoptosis may also be important for establishment and/or maintenance of persistent infections. Whereas large DNA viruses have the luxury of encoding accessory proteins whose primary function is to undermine programmed cell death pathways, it is generally thought that most RNA viruses do not encode these types of proteins. Here we report that the multifunctional capsid protein of Rubella virus is a potent inhibitor of apoptosis. The main mechanism of action was specific for Bax as capsid bound Bax and prevented Bax-induced apoptosis but did not bind Bak nor inhibit Bak-induced apoptosis. Intriguingly, interaction with capsid protein resulted in activation of Bax in the absence of apoptotic stimuli, however, release of cytochrome c from mitochondria and concomitant activation of caspase 3 did not occur. Accordingly, we propose that binding of capsid to Bax induces the formation of hetero-oligomers that are incompetent for pore formation. Importantly, data from reverse genetic studies are consistent with a scenario in which the anti-apoptotic activity of capsid protein is important for virus replication. If so, this would be among the first demonstrations showing that blocking apoptosis is important for replication of an RNA virus. Finally, it is tempting to speculate that other slowly replicating RNA viruses employ similar mechanisms to avoid killing infected cells.
Multimeric, Multifunctional Derivatives of Poly(ethylene glycol)  [PDF]
Marina Zacchigna,Francesca Cateni,Sara Drioli,Gian Maria Bonora
Polymers , 2011, DOI: 10.3390/polym3031076
Abstract: This article reviews the use of multifunctional polymers founded on high-molecular weight poly(ethylene glycol) (PEG). The design of new PEG derivatives assembled in a dendrimer-like multimeric fashion or bearing different functionalities on the same molecule is described. Their use as new drug delivery systems based on the conjugation of multiple copies or diversely active drugs on the same biocompatible support is illustrated.
Mitochondrial Ceramide-Rich Macrodomains Functionalize Bax upon Irradiation  [PDF]
Hyunmi Lee,Jimmy A. Rotolo,Judith Mesicek,Tuula Penate-Medina,Andreas Rimner,Wen-Chieh Liao,Xianglei Yin,Govind Ragupathi,Desiree Ehleiter,Erich Gulbins,Dayong Zhai,John C. Reed,Adriana Haimovitz-Friedman,Zvi Fuks,Richard Kolesnick
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019783
Abstract: Evidence indicates that Bax functions as a “lipidic” pore to regulate mitochondrial outer membrane permeabilization (MOMP), the apoptosis commitment step, through unknown membrane elements. Here we show mitochondrial ceramide elevation facilitates MOMP-mediated cytochrome c release in HeLa cells by generating a previously-unrecognized mitochondrial ceramide-rich macrodomain (MCRM), which we visualize and isolate, into which Bax integrates.
Homogenization of a catalyst layer model for periodically distributed pore geometries in PEM fuel cells  [PDF]
Markus Schmuck,Peter Berg
Physics , 2012,
Abstract: We formally derive an effective catalyst layer model comprising the reduction of oxygen for periodically distributed pore geometries. By assumption, the pores are completely filled with water and the surrounding walls consist of catalyst particles which are attached to an electron conducting microstructure. The macroscopic transport equations are established by a multi-scale approach, based on microscopic phenomena at the pore level, and serve as a first step toward future optimization of catalyst layer designs.
A BAX/BAK and Cyclophilin D-Independent Intrinsic Apoptosis Pathway  [PDF]
Sebastián Zamorano, Diego Rojas-Rivera, Fernanda Lisbona, Valentina Parra, Felipe A. Court, Rosario Villegas, Emily H. Cheng, Stanley J. Korsmeyer, Sergio Lavandero, Claudio Hetz
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037782
Abstract: Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO) cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-XL overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD) expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria.
THE SENSITIVITY OF THE CATALYST EFFECTIVENESS FACTOR TO PORE SIZE DISTRIBUTION
Brazilian Journal of Chemical Engineering , 1997, DOI: 10.1590/S0104-66321997000300012
Abstract: a model is proposed for the average effective diffusivity for an arbitrary pore size distribution. it is shown that the average diffusivity must also depend on the distribution of the catalyst sites. the reaction diffusivity is compared with the average diffusivities defined by wakao and smith (1962) and johnson and stewart (1965). for the methanol dehydration and n-butene isomerization, the reaction diffusivity gives a better estimation of the effectiveness factor than the other models
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.