Induction of Apoptosis by Targeting the Microtubule Network: Using HIV Tat as a Model System

2003 ◽  
Author(s):  
Dan Chen ◽  
Qiang Zhou
Cell Cycle ◽  
2013 ◽  
Vol 12 (5) ◽  
pp. 743-752 ◽  
Author(s):  
Yingyu Ma ◽  
Wei-Dong Yu ◽  
Alejandro A. Hidalgo ◽  
Wei Luo ◽  
Remi Delansorne ◽  
...  

Genes ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 145 ◽  
Author(s):  
Peter Polčic ◽  
Marek Mentel

Proteins of the Bcl-2 family regulate the permeabilization of the mitochondrial outer membrane that represents a crucial irreversible step in the process of induction of apoptosis in mammalian cells. The family consists of both proapoptotic proteins that facilitate the membrane permeabilization and antiapoptotic proteins that prevent it in the absence of an apoptotic signal. The molecular mechanisms, by which these proteins interact with each other and with the mitochondrial membranes, however, remain under dispute. Although yeast do not have apparent homologues of these apoptotic regulators, yeast cells expressing mammalian members of the Bcl-2 family have proved to be a valuable model system, in which action of these proteins can be effectively studied. This review focuses on modeling the activity of proapoptotic as well as antiapoptotic proteins of the Bcl-2 family in yeast.


2020 ◽  
Author(s):  
Pingtao Tang ◽  
Jharna R. Das ◽  
Jinliang Li ◽  
Jing Yu ◽  
Patricio E. Ray

AbstractBackgroundModern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments.ObjectivesTo define whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN.Design/MethodsAn HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vectors (rAd-Tat). rAd-Tat and LacZ control vectors (2 × 109) were expressed in the kidney of newborn wild type and HIV-transgenic (Tg26) FVB/N mice without significant proteinuria (n = 5 - 8 per group). Mice were sacrificed 7 and 35 days later to assess their renal outcome, the expression of HIV-genes and growth factors, and markers of cell growth and differentiation by RT-qPCR, immunohistochemistry, and/or Western blots.ResultsHIV-Tat induced the expression of HIV-1 genes (env) and heparin binding growth factors in the kidney of HIV-Tg26 mice, and precipitated HIVAN in the first month of life. No significant renal changes were detected in wild type mice infected with rAd-Tat vectors, suggesting that HIV-Tat alone does not induce renal disease.ConclusionThis new mouse model of childhood HIVAN highlights the critical role that HIV-Tat plays in the pathogenesis of HIVAN, and could be used to study the pathogenesis and treatment of HIVAN in children and adolescents.Summary statementWe developed a new inducible mouse model system of childhood HIV-associated nephropathy, and demonstrated that HIV-Tat plays a critical role in this renal disease acting in synergy with other HIV-1 genes and heparin binding cytokines.


Author(s):  
D. C. Williams ◽  
D. E. Outka

Many studies have shown that the Golgi apparatus is involved in a variety of synthetic activities, and probably no Golgi product is more elaborate than the scales produced by various kinds of phytoflagellates. The formation of calcified scales (coccoliths, Fig. 1,2) of the coccolithophorid phytoflagellates provides a particularly interesting model system for the study of biological mineralization, and the sequential formation of Golgi products.The coccoliths of Hymenomonas carterae consist of a scale-like base (Fig. 2 and 4, b) with a highly structured calcified (CaCO3) rim composed of two distinct elements which alternate about the base periphery (Fig. 1 and 3, A, B). Each element is enveloped by a sheath-like organic matrix (Fig. 3; Fig. 4, m).


Author(s):  
Masako Osumi ◽  
Misuzu Nagano ◽  
Hiroko Kazama

We have found that microbodies appeared profusely together with a remarkable increase in catalase activity in normal alkane-grown cells of hydrocarbon-utilizing Candida yeasts, and that the microbodies multiplied by division in these cells. These features of Candida yeasts seem to provide a useful model system for studies on the biogenesis of the microbody. Subsequently, we have succeeded in isolation of Candida microbodies in an apparently native state, as judged biochemically and morphologically. The presence of DNA in the purified microbody fraction thus obtained was proved by the diphenylamine method. DNA molecule of about 15 urn in contour length was released from an isolated microbody. The physicochemical analyses of the microbody DNA revealed that its buoyant density differed from nuclear and mitochondrial DNAs. All these results lead us to the possibility that there is a novel type of DNA in microbodies.


Author(s):  
M.J. Witcomb ◽  
U. Dahmen ◽  
K.H. Westmacott

Cu-Cr age-hardening alloys are of interest as a model system for the investigation of fcc/bcc interface structures. Several past studies have investigated the morphology and interface structure of Cr precipitates in a Cu matrix (1-3) and good success has been achieved in understanding the crystallography and strain contrast of small needle-shaped precipitates. The present study investigates the effect of small amounts of phosphorous on the precipitation behavior of Cu-Cr alloys.The same Cu-0.3% Cr alloy as was used in earlier work was rolled to a thickness of 150 μm, solution treated in vacuum at 1050°C for 1h followed by quenching and annealing for various times at 820 and 863°C.Two laths and their corresponding diffraction patterns in an alloy aged 2h at 820°C are shown in correct relative orientation in Fig. 1. To within the limit of accuracy of the diffraction patterns the orientation relationship was that of Kurdjumov-Sachs (KS), i.e. parallel close-packed planes and directions.


Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.


Author(s):  
J. T. Ellzey ◽  
D. Borunda ◽  
B. P. Stewart

Genetically alcohol deficient deer mice (ADHN/ADHN) (obtained from the Peromyscus Genetic Stock Center, Univ. of South Carolina) lack hepatic cytosolic alcohol dehydrogenase. In order to determine if these deer mice would provide a model system for an ultrastructural study of the effects of ethanol on hepatocyte organelles, 75 micrographs of ADH+ adult male deer mice (n=5) were compared with 75 micrographs of ADH− adult male deer mice (n=5). A morphometric analysis of mitochondrial and peroxisomal parameters was undertaken.The livers were perfused with 0.1M HEPES buffer followed by 0.25% glutaraldehyde and 2% sucrose in 0.1M HEPES buffer (4C), removed, weighed and fixed by immersion in 2.5% glutaraldehyde in 0.1M HEPES buffer, pH 7.4, followed by a 3,3’ diaminobenzidine (DAB) incubation, postfixation with 2% OsO4, en bloc staining with 1% uranyl acetate in 0.025M maleate-NaOH buffer, dehydrated, embedded in Poly/Bed 812-BDMA epon resin, sectioned and poststained with uranyl acetate and lead citrate. Photographs were taken on a Zeiss EM-10 transmission electron microscope, scanned with a Howtek personal color scanner, analyzed with OPTIMAS 4.02 software on a Gateway2000 4DX2-66V personal computer and stored in Excel 4.0.


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