The Experts below are selected from a list of 7601718 Experts worldwide ranked by ideXlab platform
Jie Zhang - One of the best experts on this subject based on the ideXlab platform.
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golph3 mediated golgi stress response in modulating N2a Cell death upon oxygen glucose deprivation and reoxygenation injury
Molecular Neurobiology, 2016Co-Authors: Hong You, Xiangqi Tang, Zheng Jiang, Shiyu Chen, Yang Chen, Jie ZhangAbstract:Increasing evidence implicating that the organelle-dependent initiation of Cell death merits further research. The evidence also implicates Golgi as a sensor and common downstream-effector of stress signals in Cell death pathways, and it undergoes disassembly and fragmentation during apoptosis in several neurological disorders. It has also been reported that during apoptotic Cell death, there is a cross talk between ER, mitochondria, and Golgi. Thus, we hypothesized that Golgi might trigger death signals during oxidative stress through its own machinery. The current study found that GOLPH3, an outer membrane protein of the Golgi complex, was significantly upregulated in N2a Cells upon oxygen-glucose deprivation and reoxygenation (OGD/R), positioning from the compact perinuclear ribbon to dispersed vesicle-like structures throughout the cytoplasm. Additionally, elevated GOLPH3 promoted a stress-induced conversion of the LC3 subunit I to II and reactive oxygen species (ROS) production in long-term OGD/R groups. The collective data indicated that GOLPH3 not only acted as a sensor of Golgi stress for its prompt upregulation during oxidative stress but also as an initiator that triggered and propagated specific Golgi stress signals to downstream effectors. This affected ROS production and stress-related autophagy and finally controlled the entry into apoptosis. The data also supported the hypothesis that the Golgi apparatus could be an ideal target for stroke, neurodegenerative diseases, or cancer therapy through its own functional proteins.
Hong You - One of the best experts on this subject based on the ideXlab platform.
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golph3 mediated golgi stress response in modulating N2a Cell death upon oxygen glucose deprivation and reoxygenation injury
Molecular Neurobiology, 2016Co-Authors: Hong You, Xiangqi Tang, Zheng Jiang, Shiyu Chen, Yang Chen, Jie ZhangAbstract:Increasing evidence implicating that the organelle-dependent initiation of Cell death merits further research. The evidence also implicates Golgi as a sensor and common downstream-effector of stress signals in Cell death pathways, and it undergoes disassembly and fragmentation during apoptosis in several neurological disorders. It has also been reported that during apoptotic Cell death, there is a cross talk between ER, mitochondria, and Golgi. Thus, we hypothesized that Golgi might trigger death signals during oxidative stress through its own machinery. The current study found that GOLPH3, an outer membrane protein of the Golgi complex, was significantly upregulated in N2a Cells upon oxygen-glucose deprivation and reoxygenation (OGD/R), positioning from the compact perinuclear ribbon to dispersed vesicle-like structures throughout the cytoplasm. Additionally, elevated GOLPH3 promoted a stress-induced conversion of the LC3 subunit I to II and reactive oxygen species (ROS) production in long-term OGD/R groups. The collective data indicated that GOLPH3 not only acted as a sensor of Golgi stress for its prompt upregulation during oxidative stress but also as an initiator that triggered and propagated specific Golgi stress signals to downstream effectors. This affected ROS production and stress-related autophagy and finally controlled the entry into apoptosis. The data also supported the hypothesis that the Golgi apparatus could be an ideal target for stroke, neurodegenerative diseases, or cancer therapy through its own functional proteins.
Li Ren - One of the best experts on this subject based on the ideXlab platform.
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melatonin ameliorates endoplasmic reticulum stress in N2a neuroblastoma Cell hypoxia reoxygenation injury by activating the ampk pak2 pathway
Cell Stress & Chaperones, 2019Co-Authors: Jin Xing, Chaobo Liu, Zilong Wei, Zhihan Wang, Liang Zhao, Li RenAbstract:Endoplasmic reticulum (ER) stress has been identified as a primary factor involved in brain ischemia-reperfusion injury progression. p21-activated kinase 2 (Pak2) is a novel ER function regulator. The aim of our study is to explore the influence of Pak2 on ER stress and determine whether melatonin attenuates ER stress-mediated Cell death by modulating Pak2 expression in vitro using N2a Cells. The results of our study demonstrated that hypoxia-reoxygenation (HR) injury repressed the levels of Pak2, an effect that was accompanied by activation of ER stress. In addition, decreased Pak2 was associated with oxidative stress, calcium overload, and caspase-12-mediated apoptosis activation in HR-treated N2a Cells. Interestingly, melatonin treatment reversed the decreased Pak2 expression under HR stress. Knockdown of Pak2 abolished the protective effects of melatonin on ER stress, oxidative stress, and caspase-12-related N2a Cells death. Additionally, we found that Pak2 was regulated by melatonin via the AMPK pathway; inhibition of AMPK prevented melatonin-mediated Pak2 upregulation, a result that was accompanied by an increase in N2a Cell death. Altogether, these results identify the AMPK-Pak2 axis as a new signaling pathway responsible for ER stress and N2a Cell viability under HR injury. Modulation of the AMPK-Pak2 cascade via supplementation of melatonin might be considered an effective approach to attenuate reperfusion-mediated N2a Cell damage via repression of ER stress.
Giuseppe Legname - One of the best experts on this subject based on the ideXlab platform.
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Synthetic prions with novel strain-specified properties
PLoS Pathogens, 2015Co-Authors: Fabio Moda, Suzana Aulic, Edoardo Bistaffa, Ilaria Campagnani, Tommaso Virgilio, Antonio Indaco, Luisa Palamara, Olivier Andréoletti, Fabrizio Tagliavini, Giuseppe LegnameAbstract:Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrPSc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrPSc were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a Cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties.
Sandra Dessì - One of the best experts on this subject based on the ideXlab platform.
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In vitro synergistic anti-prion effect of cholesterol ester modulators in combination with chlorpromazine and quinacrine
Central European Journal of Biology, 2010Co-Authors: Christina D. Orrù, M. Dolores Cannas, Sarah Vascellari, Fabrizio Angius, Pier Luigi Cocco, Claudia Norfo, Antonella Mandas, Paolo La Colla, Giacomo Diaz, Sandra DessìAbstract:Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral Cells of sheep susceptible-to or suffering-from Scrapie were characterized by an altered cholesterol homeostasis, and that drugs affecting cholesterol ester pool were endowed with selective anti-prion activity in N2a Cell lines infected with the 22L and RML prion strains. In these prion-infected N2a Cell lines, we now report increased anti-prion activity of dual-drug combinations consisting of cholesterol ester modulators associated with prion inhibitors. Synergism was obtained with the cholesterol ester modulators everolimus, pioglitazone, progesterone, and verapamil associated with the anti-prion chlorpromazine, and with everolimus and pioglitazone associated with the anti-prion quinacrine. In addition, comparative lipid analyses in prion-infected vs. uninfected N2a Cells, demonstrated a derangement of type and distribution of cholesterol ester, free cholesterol, and triglyceride pools in the infected Cells. Single-drug treatments differently affected synthesis of the various lipid forms, whereas combined drug treatments appeared to restore a lipid profile similar to that of the untreated-uninfected Cells. We conclude that the anti-prion synergistic effects of cholesterol ester modulators associated with the cholesterol-interfering anti-prion drugs chlorpromazine and quinacrine may arise from the ability of combined drugs to re-establish lipid homeostasis in the prion-infected Cells. Overall, these data suggest that inhibition of prion replication can be readily potentiated by combinatorial drug treatments and that steps of cholesterol/cholesterol ester metabolism may represent suitable targets.
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In vitro synergistic anti-prion effect of cholesterol ester modulators
Nature Precedings, 2009Co-Authors: Christina D. Orrù, M. Dolores Cannas, Sarah Vascellari, Fabrizio Angius, Pier Luigi Cocco, Claudia Norfo, Antonella Mandas, Paolo La Colla, Sandra Dessì, Alessandra PaniAbstract:Background. Our studies on the role of cholesterol in prion infection/replication showed that brains and peripheral Cells of sheep susceptible to or suffering from Scrapie were characterized by an altered cholesterol homeostasis compared to animals with a scrapie-resistant genotype, and that drugs influencing cholesterol esterification were endowed with selective anti-prion activity in N2a Cell lines infected with the 22L and RML prion strains. Results. In prion-infected N2a Cell lines we now report increased anti-prion activity of dual-drug combinations consisting of cholesterol ester modulators associated with prion inhibitors Synergism was obtained with the cholesterol ester modulators everolimus, pioglitazone, progesterone, and verapamil associated with the anti-prion chlorpromazine, and with everolimus and pioglitazone associated with the anti-prion quinacrine. Comparative lipid analyses in prion-infected and non-infected N2a Cells by colorimetric, enzymatic, and chemical means, clearly demonstrated a derangement of type and distribution of cholesterol esters, free cholesterol, and triglycerides in the infected N2a Cells. Although single-drug treatments influenced lipid syntheses, only the combined-drug treatments appeared to restore a lipid profile similar to that of untreated-uninfected Cells. Conclusions. We conclude that the anti-prion synergistic effect of cholesterol ester modulators with the cholesterol metabolism interfering anti-prion drugs chlorpromazine and quinacrine may arise from the ability of combined drugs to re-establish the intraCellular lipid profile of untreated-uninfected Cells. Overall, these data suggest that inhibition of prion replication can be readily potentiated by combinatorial drug treatments, and that steps of cholesterol/cholesterol ester metabolism may represent suitable targets.
