keyword
MENU ▼
Read by QxMD icon Read
search

bryostatin

keyword
https://www.readbyqxmd.com/read/27994072/hiv-1-latency-reversing-agents-prostratin-and-bryostatin-1-induce-blood-brain-barrier-disruption-inflammation-and-modulate-leukocyte-adhesion-transmigration
#1
Clélia Dental, Alizé Proust, Michel Ouellet, Corinne Barat, Michel J Tremblay
A shock-and-kill approach involving the simultaneous treatment of HIV-1-infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1-infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3...
December 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27993846/nonnucleoside-reverse-transcriptase-inhibitors-reduce-hiv-1-virus-production-from-latently-infected-resting-cd4-t-cells-following-latency-reversal
#2
Jennifer M Zerbato, Gilda Tachedjian, Nicolas Sluis-Cremer
Therapeutic strategies that target the latent HIV-1 reservoir in resting CD4+ T cells of infected-individuals are always administered in the presence of combination antiretroviral therapy. Using a primary cell of HIV-1 latency, we evaluated whether different antiviral drug classes affected latency reversal (as assessed by extracellular virus production) by anti-CD3/CD28 monoclonal antibodies or by bryostatin 1. We found that the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine significantly decreased HIV-1 production by ≥ 1 log...
December 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27978828/integrin-fak-signaling-rapidly-and-potently-promotes-mitochondrial-function-through-stat3
#3
Nishant P Visavadiya, Matthew P Keasey, Vladislav Razskazovskiy, Kalpita Banerjee, Cuihong Jia, Chiharu Lovins, Gary L Wright, Theo Hagg
BACKGROUND: STAT3 is increasingly becoming known for its non-transcriptional regulation of mitochondrial bioenergetic function upon activation of its S727 residue (S727-STAT3). Lengthy mitochondrial dysfunction can lead to cell death. We tested whether an integrin-FAK-STAT3 signaling pathway we recently discovered regulates mitochondrial function and cell survival, and treatments thereof. METHODS: Cultured mouse brain bEnd5 endothelial cells were treated with integrin, FAK or STAT3 inhibitors, FAK siRNA, as well as integrin and STAT3 activators...
December 15, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27941949/in-vitro-effects-of-the-small-molecule-protein-kinase-c-agonists-on-hiv-latency-reactivation
#4
Jessica Brogdon, Widade Ziani, Xiaolei Wang, Ronald S Veazey, Huanbin Xu
The persistence of latently HIV-infected cellular reservoirs represents the major obstacle to virus eradication in patients under antiretroviral therapy (ART). Cure strategies to eliminate these reservoirs are thus needed to reactivate proviral gene expression in latently infected cells. In this study, we tested optimal concentrations of PKC agonist candidates (PEP005/Ingenol-3-angelate, prostratin, bryostatin-1, and JQ1) to reactivate HIV latency in vitro, and examined their effects on cell survival, activation and epigenetic histone methylation after treatment alone or in combination in cell line and isolated CD4 T cells from SIV-infected macaques...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27785754/nuclear-accumulation-of-histone-deacetylase-4-hdac4-exerts-neurotoxicity-in-models-of-parkinson-s-disease
#5
Qimei Wu, Xiaoyu Yang, Lei Zhang, Yu Zhang, Linyin Feng
Histone deacetylase 4 (HDAC4) is a class II HDAC which is highly expressed in the brain. Previous reports have shown that HDAC4 is essential for normal brain physiology and its deregulation leads to several neurodegenerative disorders. However, it remains unclear whether dysregulation of HDAC4 is specifically involved in the development of Parkinson's disease. In this study, we demonstrate that intracellular trafficking of HDAC4 is important in regulating dopaminergic cell death. While HDAC4 normally localizes to the cytoplasm, nuclear accumulation of HDAC4 was observed in dopaminergic neurons overexpressing A53T mutant α-synuclein treated with MPP(+)/MPTP in vitro and in vivo...
October 26, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27714213/the-evolution-of-a-stereoselective-synthesis-of-the-c1-c16-fragment-of-bryostatins
#6
Matthew Ball, Anne Baron, Ben Bradshaw, Raphaël Dumeunier, Matthew O'Brien, Eric J Thomas
The development of a synthesis of the C1-C16 fragment of bryostatins in which the key step is a stereoselective oxy-Michael reaction used to assemble the cis-2,6-disubstituted tetrahydropyran with the exocyclic alkene already installed, is described. Following early work using Stille reactions to prepare precursors for oxy-Michael reactions, a more efficient route was devised based on a ketophosphonate-aldehyde condensation to prepare the key dienone. Synthesis of the aldehyde required for the ketophosphonate condensation involved the highly stereoselective addition of a diorganocuprate derived from allylmagnesium bromide and copper(i) iodide to the methyl 5-hydroxyhex-2-ynoate prepared by ring-opening of a protected glycidol using lithiated methyl propiolate...
October 12, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27713589/replacement-of-the-bryostatin-a-and-b-pyran-rings-with-phenyl-rings-leads-to-loss-of-high-affinity-binding-with-pkc
#7
Mark E Petersen, Noemi Kedei, Nancy E Lewin, Peter M Blumberg, Gary E Keck
We describe a convergent synthesis of a bryostatin analogue in which the natural A- and B-ring pyrans have been replaced by phenyl rings. The new analogue exhibited PMA like behavior in cell assays, but failed to maintain high affinity binding for PKC, despite retaining an unaltered C-ring 'binding domain'.
October 19, 2016: Tetrahedron Letters
https://www.readbyqxmd.com/read/27676096/evaluation-of-chromane-based-bryostatin-analogues-prepared-via-hydrogen-mediated-c-c-bond-formation-potency-does-not-confer-bryostatin-like-biology
#8
John M Ketcham, Ivan Volchkov, Te-Yu Chen, Peter M Blumberg, Noemi Kedei, Nancy E Lewin, Michael J Krische
The synthesis and biological evaluation of chromane-containing bryostatin analogues WN-2-WN-7 and the previously reported salicylate-based analogue WN-8 are described. Analogues WN-2-WN-7 are prepared through convergent assembly of the chromane-containing fragment B-I with the "binding domain" fragment A-I or its C26-des-methyl congener, fragment A-II. The synthesis of fragment B-I features enantioselective double C-H allylation of 1,3-propanediol to form the C2-symmetric diol 3 and Heck cyclization of bromo-diene 5 to form the chromane core...
October 12, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27664855/comparative-analysis-of-the-anti-chikungunya-virus-activity-of-novel-bryostatin-analogs-confirms-the-existence-of-a-pkc-independent-mechanism
#9
Rana Abdelnabi, Daryl Staveness, Katherine E Near, Paul A Wender, Leen Delang, Johan Neyts, Pieter Leyssen
Previously, we reported that salicylate-based analogs of bryostatin protect cells from chikungunya virus (CHIKV)-induced cell death. Interestingly, 'capping' the hydroxyl group at C26 of a lead bryostatin analog, a position known to be crucial for binding to and modulation of protein kinase C (PKC), did not abrogate the anti-CHIKV activity of the scaffold, putatively indicating the involvement of a pathway independent of PKC. The work detailed in this study demonstrates that salicylate-derived analog 1 and two capped analogs (2 and 3) are not merely cytoprotective compounds, but act as selective and specific inhibitors of CHIKV replication...
September 21, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27590822/lack-of-overt-genome-reduction-in-the-bryostatin-producing-bryozoan-symbiont-candidatus-endobugula-sertula
#10
Ian J Miller, Niti Vanee, Stephen S Fong, Grace E Lim-Fong, Jason C Kwan
: The uncultured bacterial symbiont "Candidatus Endobugula sertula" is known to produce cytotoxic compounds called bryostatins, which protect the larvae of its host, Bugula neritina The symbiont has never been successfully cultured, and it was thought that its genome might be significantly reduced. Here, we took a shotgun metagenomics and metatranscriptomics approach to assemble and characterize the genome of "Ca Endobugula sertula." We found that it had specific metabolic deficiencies in the biosynthesis of certain amino acids but few other signs of genome degradation, such as small size, abundant pseudogenes, and low coding density...
November 15, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27545045/single-cell-characterization-of-viral-translation-competent-reservoirs-in-hiv-infected-individuals
#11
Amy E Baxter, Julia Niessl, Rémi Fromentin, Jonathan Richard, Filippos Porichis, Roxanne Charlebois, Marta Massanella, Nathalie Brassard, Nirmin Alsahafi, Gloria-Gabrielle Delgado, Jean-Pierre Routy, Bruce D Walker, Andrés Finzi, Nicolas Chomont, Daniel E Kaufmann
HIV cure efforts are hampered by limited characterization of the cells supporting HIV replication in vivo and inadequate methods for quantifying the latent viral reservoir in patients receiving antiretroviral therapy. We combine fluorescent in situ RNA hybridization with detection of HIV protein and flow cytometry, enabling detection of 0.5-1 gag-pol mRNA(+)/Gag protein(+)-infected cells per million. In the peripheral blood of untreated persons, active HIV replication correlated with viremia and occurred in CD4 T cells expressing T follicular helper cell markers and inhibitory co-receptors...
September 14, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27494208/synthesis-and-biological-evaluation-of-several-bryostatin-analogues-bearing-a-diacylglycerol-lactone-c-ring
#12
David O Baumann, Kevin M McGowan, Noemi Kedei, Megan L Peach, Peter M Blumberg, Gary E Keck
As an initial step in designing a simplified bryostatin hybrid molecule, three bryostatin analogues bearing a diacylglycerol lactone-based C-ring, which possessed the requisite pharmacophores for binding to protein kinase C (PKC) together with a modified bryostatin-like A- and B-ring region, were synthesized and evaluated. Merle 46 and Merle 47 exhibited binding affinity to PKC alpha with Ki values of 7000 ± 990 and 4940 ± 470 nM, respectively. Reinstallation of the trans-olefin and gem-dimethyl group present in bryostatin 1 in Merle 48 resulted in improved binding affinity, 363 ± 42 nM...
September 2, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27472877/pkc-activation-counteracts-adam10-deficit-in-hud-silenced-neuroblastoma-cells
#13
Nicoletta Marchesi, Marialaura Amadio, Claudia Colombrita, Stefano Govoni, Antonia Ratti, Alessia Pascale
Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells...
September 6, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27428432/the-effect-of-latency-reversal-agents-on-primary-cd8-t-cells-implications-for-shock-and-kill-strategies-for-human-immunodeficiency-virus-eradication
#14
Victoria E Walker-Sperling, Christopher W Pohlmeyer, Patrick M Tarwater, Joel N Blankson
Shock and kill strategies involving the use of small molecules to induce viral transcription in resting CD4+ T cells (shock) followed by immune mediated clearance of the reactivated cells (kill), have been proposed as a method of eliminating latently infected CD4+ T cells. The combination of the histone deacetylase (HDAC) inhibitor romidepsin and protein kinase C (PKC) agonist bryostatin-1 is very effective at reversing latency in vitro. However, we found that primary HIV-1 specific CD8+ T cells were not able to eliminate autologous resting CD4+ T cells that had been reactivated with these drugs...
June 2016: EBioMedicine
https://www.readbyqxmd.com/read/27372854/oocyte-activation-and-latent-hiv-1-reactivation-ampk-as-a-common-mechanism-of-action-linking-the-beginnings-of-life-and-the-potential-eradication-of-hiv-1
#15
Jahahreeh Finley
In all mammalian species studied to date, the initiation of oocyte activation is orchestrated through alterations in intracellular calcium (Ca(2+)) signaling. Upon sperm binding to the oocyte plasma membrane, a sperm-associated phospholipase C (PLC) isoform, PLC zeta (PLCζ), is released into the oocyte cytoplasm. PLCζ hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce diacylglycerol (DAG), which activates protein kinase C (PKC), and inositol 1,4,5-trisphosphate (IP3), which induces the release of Ca(2+) from endoplasmic reticulum (ER) Ca(2+) stores...
August 2016: Medical Hypotheses
https://www.readbyqxmd.com/read/27330081/protein-kinase-c%C3%AF%C2%B5-pkc%C3%AF%C2%B5-promotes-synaptogenesis-through-membrane-accumulation-of-the-postsynaptic-density-protein-psd-95
#16
Abhik Sen, Jarin Hongpaisan, Desheng Wang, Thomas J Nelson, Daniel L Alkon
Protein kinase Cϵ (PKCϵ) promotes synaptic maturation and synaptogenesis via activation of synaptic growth factors such as BDNF, NGF, and IGF. However, many of the detailed mechanisms by which PKCϵ induces synaptogenesis are not fully understood. Accumulation of PSD-95 to the postsynaptic density (PSD) is known to lead to synaptic maturation and strengthening of excitatory synapses. Here we investigated the relationship between PKCϵ and PSD-95. We show that the PKCϵ activators dicyclopropanated linoleic acid methyl ester and bryostatin 1 induce phosphorylation of PSD-95 at the serine 295 residue, increase the levels of PSD-95, and enhance its membrane localization...
August 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27128726/effects-of-exercise-and-bryostatin-1-on-serotonin-dynamics-after-cerebral-infarction
#17
Kenmei Mizutani, Shigeru Sonoda, Hideaki Wakita, Hideto Okazaki, Yoshimitsu Katoh, Takeshi Chihara, Kan Shimpo
Although it has been suggested that the combination of exercise and bryostatin-1 administration may induce greater functional recovery than exercise alone, the detailed molecular mechanisms are not well known. Here, we examined the relationship between this combination treatment and monoamine dynamics in the cerebral cortex peri-infarction area to promote our understanding of these molecular mechanisms. Experimental cerebral cortex infarctions were produced by photothrombosis in rats. Voluntary exercise was initiated 2 days after surgery...
June 15, 2016: Neuroreport
https://www.readbyqxmd.com/read/27068183/isolation-analytical-measurements-and-cell-line-studies-of-the-iron-bryostatin-1-complex
#18
Sydney Plummer, Thomas Manning, Tess Baker, Tysheon McGreggor, Mehulkumar Patel, Greg Wylie, Dennis Phillips
Bryostatin-1 is a marine natural product that has demonstrated medicinal activity in pre-clinical and clinical trials for the treatment of cancer, Alzheimer's disease, effects of stroke, and HIV. In this study, iron-bryostatin-1 was obtained using a pharmaceutical aquaculture technique developed by our lab that cultivates marine bacteria for marine natural product extraction. Analytical measurements (1)H and (13)C NMR, mass spectrometry, and flame atomic absorption were utilized to confirm the presence of an iron-bryostatin-1 complex...
May 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26991955/e-cadherin-facilitates-protein-kinase-d1-activation-and-subcellular-localization
#19
Zhuo Li, Chuanyou Zhang, Li Chen, Guosheng Li, Ling Qu, K C Balaji, Cheng Du
Protein kinase D 1 (PKD1) is a serine/threonine kinase implicated in the regulation of diverse cellular functions including cell growth, differentiation, adhesion and motility. The current model for PKD1 activation involves diacylglycerol (DAG) binding to the C1 domain of PKD1 which results in the translocation of PKD1 to subcellular membranes where PKD1 is phosphorylated and activated by protein kinase C (PKC). In this study, we have identified a novel regulation of PKD1 activation. The epithelial cell membrane protein E-cadherin physically binds to PKD1 which leads to a subcellular redistribution of PKD1...
December 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/26941170/rescue-of-synaptic-phenotypes-and-spatial-memory-in-young-fragile-x-mice
#20
Miao-Kun Sun, Jarin Hongpaisan, Daniel L Alkon
Fragile X syndrome (FXS) is characterized by synaptic immaturity, cognitive impairment, and behavioral changes. The disorder is caused by transcriptional shutdown in neurons of thefragile X mental retardation 1gene product, fragile X mental retardation protein. Fragile X mental retardation protein is a repressor of dendritic mRNA translation and its silencing leads to dysregulation of synaptically driven protein synthesis and impairments of intellect, cognition, and behavior, and FXS is a disorder that currently has no effective therapeutics...
May 2016: Journal of Pharmacology and Experimental Therapeutics
keyword
keyword
89228
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"