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Pesquisa : D02.806.250 [Categoria DeCS]
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[PMID]:29288942
[Au] Autor:Martín-Acosta P; Haider S; Amesty Á; Aichele D; Jose J; Estévez-Braun A
[Ad] Endereço:Instituto Universitario de Bio-Orgánica Antonio González (CIBICAN), Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez Nº 2, 38206, La Laguna, Tenerife, Spain.
[Ti] Título:A new family of densely functionalized fused-benzoquinones as potent human protein kinase CK2 inhibitors.
[So] Source:Eur J Med Chem;144:410-423, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A new series of 2-amino-4-phenyl-6-hydroxy-7-alkyl-pyranobenzoquinones was synthesized as ATP-competitive CK2 inhibitors. They were readily synthesized through a three-component Knoevenagel condensation-Michael addition-heterocyclization reaction from aldehydes, malononitrile, and 3-alkyl-2,5-dihydroxybenzoquinones. Some of the synthesized compounds presented interesting inhibitory activity with IC values in the submicromolar range. A structure-activity relationship study was carried out and the mode of binding was analysed by docking studies and supported by ATP competition assays.
[Mh] Termos MeSH primário: Benzoquinonas/farmacologia
Caseína Quinase II/antagonistas & inibidores
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Benzoquinonas/síntese química
Benzoquinonas/química
Caseína Quinase II/metabolismo
Sobrevivência Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Seres Humanos
Células MCF-7
Estrutura Molecular
Inibidores de Proteínas Quinases/síntese química
Inibidores de Proteínas Quinases/química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Protein Kinase Inhibitors); EC 2.7.11.1 (Casein Kinase II)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171231
[St] Status:MEDLINE


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[PMID]:29254287
[Au] Autor:Jiang L; Li H; Zhao N
[Ad] Endereço:Department of Anesthesiology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi, China.
[Ti] Título:Thymoquinone protects against cobalt chloride-induced neurotoxicity via Nrf2/GCL-regulated glutathione homeostasis.
[So] Source:J Biol Regul Homeost Agents;31(4):843-853, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:The prevalence of neurodegenerative diseases worldwide has increased dramatically in the last decades. Hypoxia and oxidative stress play a central role in the pathogenesis of neurodegenerative diseases. Thymoquinone (TQ) is a monoterpenoid hydrocarbon compound that possesses potent antioxidant activity. In the current study, we investigated the neuroprotective effects of TQ against CoCl2, a widely used hypoxia-inducing agent. We found that TQ inhibited CoCl2-indcued cytotoxicity in vitro, as reflected by an increase of cell viability and decrease of apoptosis in CoCl2-treated PC12 cells. TQ exhibited a potent protective effect against CoCl2-induced neurotoxicity in vivo, as evidenced by decreased time spent to find the platform site in the Probe trials, reduced escape latencies, decreased traveling distance and reduction of apoptotic cell death in brains in CoCl2-treated rats. CoCl2-resulted decrease of glutathione (GSH) and increase of malondialdehyde (MDA) levels were significantly inhibited by TQ. Inhibition of GSH synthesis by buthionine sulphoximine (BSO) significantly attenuated TQ-induced neuroprotective effects against CoCl2 in rats and in PC12 cells. TQ could upregulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLc) and Nrf2/glutamate-cysteine ligase modifier subunit (GCLm) pathway which contributed to antioxidant and neuroprotective effects of TQ. In summary, we found that TQ exhibited protective effects against neurotoxicity via upregulation of Nrf2/GCL signaling. Upregulation of Nrf2/GCL signaling promoted the synthesis of GSH and contributed to attenuation of oxidative stress, neuronal cell apoptosis and neurotoxicity. These data have appointed a new path toward the understanding of the neuroprotective activities of TQ.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Benzoquinonas/farmacologia
Cobalto/farmacologia
Hipóxia/prevenção & controle
Fármacos Neuroprotetores/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Butionina Sulfoximina/antagonistas & inibidores
Butionina Sulfoximina/farmacologia
Hipóxia Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Comportamento Exploratório/efeitos dos fármacos
Regulação da Expressão Gênica/efeitos dos fármacos
Glutamato-Cisteína Ligase/genética
Glutamato-Cisteína Ligase/metabolismo
Glutationa/agonistas
Glutationa/metabolismo
Seres Humanos
Hipóxia/induzido quimicamente
Hipóxia/genética
Hipóxia/patologia
Masculino
Malondialdeído/antagonistas & inibidores
Malondialdeído/metabolismo
Fator 2 Relacionado a NF-E2/genética
Fator 2 Relacionado a NF-E2/metabolismo
Células PC12
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Benzoquinones); 0 (NF-E2-Related Factor 2); 0 (Neuroprotective Agents); 0 (Nfe2l2 protein, rat); 3G0H8C9362 (Cobalt); 490-91-5 (thymoquinone); 4Y8F71G49Q (Malondialdehyde); 5072-26-4 (Buthionine Sulfoximine); EC 6.3.2.2 (GCLM protein, rat); EC 6.3.2.2 (Glutamate-Cysteine Ligase); EC 6.3.2.2. (GCLC protein, rat); EVS87XF13W (cobaltous chloride); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE


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[PMID]:29406097
[Au] Autor:Xu T; Yin J; Chen S; Zhang D; Wang H
[Ad] Endereço:State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: xutianstudent@126.com.
[Ti] Título:Elevated 8-oxo-7,8-dihydro-2'-deoxyguanosine in genome of T24 bladder cancer cells induced by halobenzoquinones.
[So] Source:J Environ Sci (China);63:133-139, 2018 Jan.
[Is] ISSN:1001-0742
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Halobenzoquinones (HBQs) are an emerging class of halogenated disinfection byproducts (DBPs) in drinking water, which raised public concerns due to potential carcinogenic effects to human bladder. Our previous work demonstrated that HBQs and hydrogen peroxide (H O ) together generated oxidative DNA damage via a metal-independent and intercalation-enhanced oxidation mechanism in vitro. This study further investigated the efficiency of various HBQs to induce oxidative DNA damage in T24 bladder cancer cells. Compared with T24 cells without treatment (3.1 lesions per 10 dG), the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) significantly increased by 1.4, 3.2, 8.8, and 9.2 times after treatment with tetrabromo-1,4-benzoquinone (TBBQ), terachloro-1,4-benzoquinone (TCBQ), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) and 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ) for 24hr, respectively. Interestingly, we found that the oxidative potency of HBQs in T24 cells (2,5-DCBQ≈2,6-DCBQ>TCBQ>TBBQ) is inconsistent with that of in vitro dsDNA oxidation (TCBQ>TBBQ>2,5-DCBQ>2,6-DCBQ), suggesting HBQs induce oxidative lesions in cellular genomic DNA probably involved with a complex mechanism.
[Mh] Termos MeSH primário: Benzoquinonas/toxicidade
Desoxiguanosina/análogos & derivados
Substâncias Perigosas/toxicidade
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Desoxiguanosina/metabolismo
Seres Humanos
Peróxido de Hidrogênio
Neoplasias da Bexiga Urinária
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Hazardous Substances); 88847-89-6 (8-oxo-7-hydrodeoxyguanosine); BBX060AN9V (Hydrogen Peroxide); G9481N71RO (Deoxyguanosine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:29406093
[Au] Autor:Ge F; Xiao Y; Yang Y; Wang W; Moe B; Li XF
[Ad] Endereço:College of Environment and Resources, Xiangtan University, Xiangtan, Hunan 411105, China. Electronic address: gefei@xtu.edu.cn.
[Ti] Título:Formation of water disinfection byproduct 2,6-dichloro-1,4-benzoquinone from chlorination of green algae.
[So] Source:J Environ Sci (China);63:1-8, 2018 Jan.
[Is] ISSN:1001-0742
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:We report that green algae in lakes and rivers can serve as precursors of halobenzoquinone (HBQ) disinfection byproducts (DBPs) produced during chlorination. Chlorination of a common green alga, Chlorella vulgaris, produced 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), the most prevalent HBQ DBP in disinfected water. Under varying pH conditions (pH6.0-9.0), 2,6-DCBQ formation ranged from 0.3 to 2.1µg/mg C with maximum formation at pH8.0. To evaluate the contribution of organic components of C. vulgaris to 2,6-DCBQ formation, we separated the organics into two fractions, the protein-rich fraction of intracellular organic matter (IOM) and the polysaccharide-laden fraction of extracellular organic matter (EOM). Chlorination of IOM and EOM produced 1.4µg/mg C and 0.7µg/mg C of 2,6-DCBQ, respectively. The IOM generated a two-fold higher 2,6-DCBQ formation potential than the EOM fraction, suggesting that proteins are potent 2,6-DCBQ precursors. This was confirmed by the chlorination of proteins extracted from C. vulgaris: the amount of 2,6-DCBQ produced is linearly correlated with the concentration of total algal protein (R =0.98). These results support that proteins are the primary precursors of 2,6-DCBQ in algae, and control of green algal bloom outbreaks in source waters is important for management of HBQ DBPs.
[Mh] Termos MeSH primário: Benzoquinonas/metabolismo
Chlorella vulgaris/fisiologia
Desinfetantes/metabolismo
Poluentes Químicos da Água/metabolismo
[Mh] Termos MeSH secundário: Benzoquinonas/análise
Clorófitas
Desinfetantes/análise
Desinfecção
Halogenação
Poluentes Químicos da Água/análise
Purificação da Água/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Disinfectants); 0 (Water Pollutants, Chemical)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:29273526
[Au] Autor:Stueber T; Meyer S; Jangra A; Hage A; Eberhardt M; Leffler A
[Ad] Endereço:Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany.
[Ti] Título:Activation of the capsaicin-receptor TRPV1 by the acetaminophen metabolite N-arachidonoylaminophenol results in cytotoxicity.
[So] Source:Life Sci;194:67-74, 2018 Feb 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: The anandamide reuptake inhibitor N-arachidonoylaminophenol (AM404) and the reactive substance N-acetyl-p-benzoquinone imine (NAPQI) are both metabolites of acetaminophen and may contribute to acetaminophen-induced analgesia by acting at TRPV1 expressed in the peripheral or central nervous system. While NAPQI slowly sensitizes and activates TRPV1 by interacting with distinct intracellular cysteine residues, detailed properties of AM404 as an agonist of TRPV1 have not yet been reported on. We explored the effects of AM404 on recombinant human TRPV1 and in rodent dorsal root ganglion (DRG) neurons. MATERIALS AND METHODS: HEK 293 cells expressing different isoforms of recombinant TRPV1 and rodent DRG neurons were employed for patch clamp and calcium imaging experiments. Cytotoxicity was assessed by propidium iodide and Annexin V staining on TRPV1-HEK 293 cells and with trypan blue staining on DRG neurons. KEY FINDINGS: AM404 activates hTRPV1 at concentrations >1µM and in a concentration-dependent manner. AM404 also potentiates TRPV1-mediated currents evoked by heat and anandamide. Moreover, AM404-evoked currents are potentiated by NAPQI. While the partly capsaicin-insensitive rabbit (o) TRPV1 fails to respond to AM404, AM404-sensitivity is restored by insertion of the capsaicin binding-domain of rat TRPV1 into oTRPV1. In DRG neurons, AM404-evoked calcium influx as well as cell death is mediated by TRPV1. SIGNIFICANCE: AM404 gates TRPV1 by interacting with the vanilloid-binding site, and TRPV1 is the main receptor for AM404 in DRG neurons. While direct activation of TRPV1 requires high concentrations of AM404, it is possible that synergistic effects of AM404 with further TRPV1-agonists may occur at clinically relevant concentrations.
[Mh] Termos MeSH primário: Acetaminofen/farmacologia
Analgésicos não Entorpecentes/farmacologia
Ácidos Araquidônicos/farmacologia
Gânglios Espinais/efeitos dos fármacos
Canais de Cátion TRPV/metabolismo
[Mh] Termos MeSH secundário: Acetaminofen/metabolismo
Analgesia
Analgésicos não Entorpecentes/metabolismo
Animais
Ácidos Araquidônicos/metabolismo
Benzoquinonas/metabolismo
Capsaicina/farmacologia
Gânglios Espinais/citologia
Células HEK293
Seres Humanos
Iminas/metabolismo
Camundongos Endogâmicos C57BL
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Coelhos
Ratos Sprague-Dawley
Fármacos do Sistema Sensorial/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Analgesics, Non-Narcotic); 0 (Arachidonic Acids); 0 (Benzoquinones); 0 (Imines); 0 (Sensory System Agents); 0 (TRPV Cation Channels); 0 (TRPV1 protein, human); 362O9ITL9D (Acetaminophen); G6S9BN13TI (N-acetyl-4-benzoquinoneimine); S07O44R1ZM (Capsaicin); XVJ94H0U21 (N-(4-hydroxyphenyl)arachidonylamide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171224
[St] Status:MEDLINE


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[PMID]:28463500
[Au] Autor:Kobylarz MJ; Heieis GA; Loutet SA; Murphy MEP
[Ad] Endereço:The Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia , Vancouver, British Columbia V6T 1Z3; Canada.
[Ti] Título:Iron Uptake Oxidoreductase (IruO) Uses a Flavin Adenine Dinucleotide Semiquinone Intermediate for Iron-Siderophore Reduction.
[So] Source:ACS Chem Biol;12(7):1778-1786, 2017 Jul 21.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many pathogenic bacteria including Staphylococcus aureus use iron-chelating siderophores to acquire iron. Iron uptake oxidoreductase (IruO), a flavin adenine dinucleotide (FAD)-containing nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase from S. aureus, functions as a reductase for IsdG and IsdI, two paralogous heme degrading enzymes. Also, the gene encoding for IruO was shown to be required for growth of S. aureus on hydroxamate siderophores as a sole iron source. Here, we show that IruO binds the hydroxamate-type siderophores desferrioxamine B and ferrichrome A with low micromolar affinity and in the presence of NADPH, Fe(II) was released. Steady-state kinetics of Fe(II) release provides k /K values in the range of 600 to 7000 M s for these siderophores supporting a role for IruO as a siderophore reductase in iron utilization. Crystal structures of IruO were solved in two distinct conformational states mediated by the formation of an intramolecular disulfide bond. A putative siderophore binding site was identified adjacent to the FAD cofactor. This site is partly occluded in the oxidized IruO structure consistent with this form being less active than reduced IruO. This reduction in activity could have a physiological role to limit iron release under oxidative stress conditions. Visible spectroscopy of anaerobically reduced IruO showed that the reaction proceeds by a single electron transfer mechanism through an FAD semiquinone intermediate. From the data, a model for single electron siderophore reduction by IruO using NADPH is described.
[Mh] Termos MeSH primário: Benzoquinonas/química
Flavina-Adenina Dinucleotídeo/química
Ferro/metabolismo
Oxirredutases/metabolismo
Sideróforos/metabolismo
[Mh] Termos MeSH secundário: Anaerobiose
Sítios de Ligação
Clonagem Molecular
Cristalografia por Raios X
Cinética
Modelos Moleculares
NADP/química
Oxirredução
Oxirredutases/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Siderophores); 146-14-5 (Flavin-Adenine Dinucleotide); 3225-29-4 (semiquinone radicals); 53-59-8 (NADP); E1UOL152H7 (Iron); EC 1.- (Oxidoreductases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.1021/acschembio.7b00203


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[PMID]:28448463
[Au] Autor:Atta MS; Almadaly EA; El-Far AH; Saleh RM; Assar DH; Al Jaouni SK; Mousa SA
[Ad] Endereço:Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt. mostafa.ataa@vet.kfs.edu.eg.
[Ti] Título:Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression.
[So] Source:Int J Mol Sci;18(5), 2017 Apr 27.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats ( = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.
[Mh] Termos MeSH primário: Antioxidantes/metabolismo
Aromatase/metabolismo
Benzoquinonas/farmacologia
Substâncias Protetoras/farmacologia
Espermatogênese/efeitos dos fármacos
Testículo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Peso Corporal/efeitos dos fármacos
Diabetes Mellitus Experimental/induzido quimicamente
Diabetes Mellitus Experimental/patologia
Glutationa/metabolismo
Masculino
Malondialdeído/metabolismo
NF-kappa B/metabolismo
Óxido Nítrico/metabolismo
Óxido Nítrico Sintase Tipo II/metabolismo
Estresse Oxidativo/efeitos dos fármacos
Ratos
Ratos Wistar
Estreptozocina/toxicidade
Superóxido Dismutase/metabolismo
Testículo/metabolismo
Testículo/patologia
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Benzoquinones); 0 (NF-kappa B); 0 (Protective Agents); 31C4KY9ESH (Nitric Oxide); 490-91-5 (thymoquinone); 4Y8F71G49Q (Malondialdehyde); 5W494URQ81 (Streptozocin); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.14.1 (Aromatase); EC 1.15.1.1 (Superoxide Dismutase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


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[PMID]:29179175
[Au] Autor:Tu RH; Li QJ; Huang Z; He Y; Meng JJ; Zheng HL; Zeng ZY; Zhong GQ
[Ad] Endereço:Department of Geriatric Cardiology, Nanning, China.
[Ti] Título:Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning.
[So] Source:Cell Physiol Biochem;44(3):982-997, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Previous studies have shown that heat shock protein 90 (HSP90)-mediated mitochondrial import of connexin 43 (Cx43) is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. METHODS: Cellular models of hypoxic postconditioning (HPC) from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS) production was assessed with the peroxide-sensitive fluorescent probe 2',7'-dichlorofluorescin in diacetate (DCFH-DA). The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA), ROS scavengers superoxide dismutase (SOD) and catalase (CAT), and small interfering RNA (siRNA) targeting Cx43 and HSP90 were also investigated. RESULTS: HPC significantly reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA) or siRNA targeting HSP90 prevented the protection of HPC and the HPC-induced association of Cx43, indicating that mitochondrial HSP90 was important for mitochondrial translocation of Cx43 during HPC. CONCLUSION: Mitochondrial HSP90 played a central role in HPC cardioprotection, and its activity was linked to the mitochondrial targeting of Cx43, the activation of which triggered ROS signaling and the subsequent reduction of redox stress. Consequently, its target gene, Bcl-2, was upregulated, and proapoptotic Bax was inhibited in the sarcolemma and mitochondria, ultimately attenuating H/R-induced cardiomyocyte apoptosis. These data reveal a novel mechanism of HPC protection.
[Mh] Termos MeSH primário: Conexina 43/metabolismo
Proteínas de Choque Térmico HSP90/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Benzoquinonas/farmacologia
Catalase/farmacologia
Hipóxia Celular
Linhagem Celular
Conexina 43/antagonistas & inibidores
Conexina 43/genética
Proteínas de Choque Térmico HSP90/antagonistas & inibidores
Proteínas de Choque Térmico HSP90/genética
Lactamas Macrocíclicas/farmacologia
Microscopia de Fluorescência
Mitocôndrias/metabolismo
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Interferência de RNA
RNA Interferente Pequeno/metabolismo
Ratos
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/química
Espécies Reativas de Oxigênio/metabolismo
Sarcolema/metabolismo
Superóxido Dismutase/farmacologia
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Connexin 43); 0 (HSP90 Heat-Shock Proteins); 0 (Lactams, Macrocyclic); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (RNA, Small Interfering); 0 (Reactive Oxygen Species); 0 (bcl-2-Associated X Protein); EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); Z3K3VJ16KU (geldanamycin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1159/000485399


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[PMID]:29191002
[Au] Autor:Nain-Perez A; Barbosa LCA; Maltha CRA; Giberti S; Forlani G
[Ad] Endereço:Department of Chemistry, Universidade Federal de Minas Gerais , Av. Pres. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901, Belo Horizonte, MG Brazil.
[Ti] Título:Tailoring Natural Abenquines To Inhibit the Photosynthetic Electron Transport through Interaction with the D1 Protein in Photosystem II.
[So] Source:J Agric Food Chem;65(51):11304-11311, 2017 Dec 27.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Abenquines are natural N-acetylaminobenzoquinones bearing amino acid residues, which act as weak inhibitors of the photosynthetic electron transport chain. Aiming to exploit the abenquine scaffold as a model for the synthesis of new herbicides targeting photosynthesis, 14 new analogues were prepared by replacing the amino acid residue with benzylamines and the acetyl with different acyl groups. The synthesis was accomplished in three steps with a 68-95% overall yield from readily available 2,5-dimethoxyaniline, acyl chlorides, and benzyl amines. Key steps include (i) acylation of the aniline, (ii) oxidation, and (iii) oxidative addition of the benzylamino moiety. The compounds were assayed for their activity as Hill inhibitors, under basal, uncoupled, or phosphorylating conditions, or excluding photosystem I. Four analogues showed high effectiveness (IC = 0.1-0.4 µM), comparable with the commercial herbicide diuron (IC = 0.3 µM). The data suggest that this class of compounds interfere at the reducing side of photosystem II, having protein D1 as the most probable target. Molecular docking studies with the plastoquinone binding site of Spinacia oleracea further strengthened this proposal.
[Mh] Termos MeSH primário: Benzoquinonas/farmacologia
Transporte de Elétrons/efeitos dos fármacos
Herbicidas/farmacologia
Fotossíntese/efeitos dos fármacos
Complexo de Proteína do Fotossistema II/metabolismo
Spinacia oleracea/metabolismo
[Mh] Termos MeSH secundário: Benzoquinonas/química
Cloroplastos/efeitos dos fármacos
Cloroplastos/metabolismo
Herbicidas/química
Simulação de Acoplamento Molecular
Spinacia oleracea/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoquinones); 0 (Herbicides); 0 (Photosystem II Protein Complex)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04624


  10 / 7480 MEDLINE  
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[PMID]:29277787
[Au] Autor:Miyamoto M; Takano M; Aoyama T; Soyama H; Ishibashi H; Kato K; Iwahashi H; Takasaki K; Kuwahara M; Matuura H; Sakamoto T; Yoshikawa T; Furuya K
[Ad] Endereço:Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan morikazu1118@hotmail.co.jp.
[Ti] Título:Phenoxodiol Increases Cisplatin Sensitivity in Ovarian Clear Cancer Cells Through XIAP Down-regulation and Autophagy Inhibition.
[So] Source:Anticancer Res;38(1):301-306, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: To investigate whether XIAP down-regulation and autophagy inhibition sensitize ovarian clear cell cancer cells to cisplatin. MATERIALS AND METHODS: The ovarian clear cancer cell line KK was used for in vitro analysis. Hydroxychloroquine (HCQ) and phenoxodiol (PXD) or embelin were used as autophagy and XIAP inhibitors, respectively. Non-specific and XIAP-specific siRNAs were transfected using Lipofectamine. Cytotoxicity was assessed by MTT assays. Protein expression was confirmed by western blotting. RESULTS: In KK, down-regulation of XIAP using specific siRNAs together with HCQ treatment enhanced the anti-tumor effect of cisplatin. Although embelin sensitized KK to cisplatin through XIAP down-regulation, it induced autophagy. However, PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition. Expression of Atg7, Atg12, and Beclin 1 was decreased after PXD treatment. CONCLUSION: PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition and could be a new candidate for ovarian clear cell carcinoma treatment.
[Mh] Termos MeSH primário: Adenocarcinoma de Células Claras/metabolismo
Antineoplásicos/farmacologia
Cisplatino/farmacologia
Isoflavonas/farmacologia
Neoplasias Ovarianas/metabolismo
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
[Mh] Termos MeSH secundário: Adenocarcinoma de Células Claras/genética
Autofagia/efeitos dos fármacos
Benzoquinonas/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Regulação para Baixo
Feminino
Seres Humanos
Neoplasias Ovarianas/genética
RNA Interferente Pequeno/genética
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Benzoquinones); 0 (Isoflavones); 0 (RNA, Small Interfering); 0 (X-Linked Inhibitor of Apoptosis Protein); 0 (XIAP protein, human); 995FT1W541 (phenoxodiol); Q20Q21Q62J (Cisplatin); SHC6U8F5ER (embelin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE



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