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Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells 总被引:2,自引:0,他引:2
Gorman AM Szegezdi E Quigney DJ Samali A 《Biochemical and biophysical research communications》2005,327(3):801-810
Cellular stress may stimulate cell survival pathways or cell death depending on its severity. 6-Hydroxydopamine (6-OHDA) is a neurotoxin that targets dopaminergic neurons that is often used to induce neuronal cell death in models of Parkinson's disease. Here we present evidence that 6-OHDA induces apoptosis in rat PC12 cells that involves release of cytochrome c and Smac/Diablo from mitochondria, caspase-3 activation, cleavage of PARP, and nuclear condensation. 6-OHDA also induced the heat shock response, leading to increased levels of Hsp25 and Hsp70. Increased Hsp25 expression was associated with cell survival. Prior heat shock or overexpression of Hsp27 (human homologue of Hsp25) delayed cytochrome c release, caspase activation, and reduced the level of apoptosis caused by 6-OHDA. We conclude that 6-OHDA induces a variety of responses in cultured PC12 cells ranging from cell survival to apoptosis, and that induction of stress proteins such as Hsp25 may protect cells from undergoing 6-OHDA-induced apoptosis. 相似文献
63.
Zarghi A Tabatabai SA Faizi M Ahadian A Navabi P Zanganeh V Shafiee A 《Bioorganic & medicinal chemistry letters》2005,15(7):1863-1865
A series of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles have been synthesized and evaluated as anticonvulsant agents. Compound 4b shows considerable anticonvulsant activity both in PTZ and MES models. It seems this effect is mediated through benzodiazepine receptors mechanism. 相似文献
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The objective of this study was to understand the behavior of particulate systems under different conditions of shear dynamics
before and after granulation and to investigate the efficiency of powder lubrication. Three drug powders, metronidazole, colloidal
bismuth citrate, and tetracycline hydrochloride, were chosen as model drugs representing noncohesive and cohesive powder systems.
Each powder was individually granulated with microcrystalline cellulose and 5%PVP as a binder. One portion from each granulation
was lubricated with different levels of magnesium stearate for 5 minutes. The powder characterization was performed on the
plain powders, nonlubricated and lubricated granules using powder rheometer equipped with a helical blade rotating and moving
under experimentally fixed set of parameters. The profiles of interaction during the forcedistance measurements indicate that
powder compresses, expands, and shears many times in a test cycle. Test profiles also clearly reveal existence of significant
differences between cohesive and noncohesive powders. In all cases lubrication normalized the overall interactive nature of
the powder by reducing peaks and valleys as observed from the profiles and reduced the frictional effect. The developed methods
are easy to perform and will allow formulation scientists to better understand powder behavior and help in predicting potential
impact of processing factors on particulate systems.
Published: October 19, 2005 相似文献
66.
The design of an industrial workstation tends to include ergonomic assessment steps based on a digital mock-up and a virtual reality setup. Lack of interaction and system fidelity is often reported as a main issue in such virtual reality applications. This limitation is a crucial issue as thorough ergonomic analysis is required for an investigation of the biomechanics. In the current study, we investigated the biomechanical responses of the shoulder joint in a simulated assembly task for comparison with the biomechanical responses in virtual environments. Sixteen male healthy novice subjects performed the task on three different platforms: real (RE), virtual (VE), and virtual environment with force feedback (VEF) with low and high precision demands. The subjects repeated the task 12 times (i.e., 12 cycles). High density electromyography from the upper trapezius and rotation angles of the shoulder joint were recorded and split into the cycles. The angular trajectories and velocity profiles of the shoulder joint angles over a cycle were computed in 3D. The inter-subject similarity in terms of normalized mutual information on kinematics and electromyography was investigated. Compared with RE the task in VE and VEF was characterized by lower kinematic maxima. The inter-subject similarity in RE compared with intra-subject similarity across the platforms was lower in terms of movement trajectories and greater in terms of trapezius muscle activation. The precision demand resulted in lower inter- and intra-subject similarity across platforms. The proposed approach identifies biomechanical differences in the shoulder joint in both VE and VEF compared with the RE platform, but these differences are less marked in VE mostly due to technical limitations of co-localizing the force feedback system in the VEF platform. 相似文献
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Shane Deegan Svetlana Saveljeva Susan E Logue Karolina Pakos-Zebrucka Sanjeev Gupta Peter Vandenabeele Mathieu JM Bertrand Afshin Samali 《Autophagy》2014,10(11):1921-1936
Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells. 相似文献
68.
Afshin Moradi 《Plasmonics (Norwell, Mass.)》2013,8(3):1509-1513
The propagation of the coupled surface plasmon-polariton modes in the metallic single-walled carbon nanotubes are investigated, taking into account the retardation effects. A simple model based on the classical electrodynamics and the two-fluid hydrodynamic theory is proposed. The dispersion relation of the surface polariton modes is obtained in order to survey the effects of the two-fluid model and the insulating dielectric media. 相似文献
69.
Shahlaei M Madadkar-Sobhani A Mahnam K Fassihi A Saghaie L Mansourian M 《Biochimica et biophysica acta》2011,1808(3):802-817
In this study, homology modeling, molecular docking and molecular dynamics simulation were performed to explore structural features and binding mechanism of some inhibitors of chemokine receptor type 5 (CCR5), and to construct a model for designing new CCR5 inhibitors for preventing HIV attachment to the host cell. A homology modeling procedure was employed to construct a 3D model of CCR5. For this procedure, the X-ray crystal structure of bovine rhodopsin (1F88A) at 2.80? resolution was used as template. After inserting the constructed model into a hydrated lipid bilayer, a 20ns molecular dynamics (MD) simulation was performed on the whole system. After reaching the equilibrium, twenty-four CCR5 inhibitors were docked in the active site of the obtained model. The binding models of the investigated antagonists indicate the mechanism of binding of the studied compounds to the CCR5 obviously. Moreover, 3D pictures of inhibitor-protein complex provided precious data regarding the binding orientation of each antagonist into the active site of this protein. One additional 20 ns MD simulation was performed on the initial structure of the CCR5-ligand 21 complex, resulted from the previous docking calculations, embedded in a hydrated POPE bilayer to explore the effects of the presence of lipid bilayer in the vicinity of CCR5-ligand complex. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes. 相似文献