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1.
Molecules ; 23(2)2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29415430

RESUMO

The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a red propolis from Chiapas State (4-EAEP) was the most potent (IC50 = 1.42 ± 0.07 µg/mL) in the TBARS assay, and selected for further studies. This extract afforded two new compounds, epoxypinocembrin chalcone (6), and an ε-caprolactone derivative (10), as well as pinostrobin (1), izalpinin (2), cinnamic acid (3), pinocembrin (4), kaempherol (5), 3,3-dimethylallyl caffeate in mixture with isopent-3-enyl caffeate (7a + 7b), 3,4-dimethoxycinnamic acid (8), rhamnetin (9) and caffeic acid (11). The HPLC profile, anti-mycobacterial, and antioxidant properties of this extract was also determined. Most of the isolated compounds were also tested by inhibition of reactive oxygen species (ROS) in challenged mouse bone marrow-derived mast cells (BMMCs), and DPPH. Their anti-inflammatory activity was evaluated by TPA, and MPO (myeloperoxidase) activity by ear edema test in mice. The most potent compounds were 7a + 7b in the TBARS assay (IC50 = 0.49 ± 0.06 µM), and 2 which restored the ROS baseline (3.5 µM). Our results indicate that 4-EAEP has anti-oxidant, and anti-inflammatory properties due to its active compounds, suggesting it has anti-allergy and anti-asthma potential.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Caproatos/química , Chalconas/química , Lactonas/química , Própole/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/imunologia , Chlorocebus aethiops , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , México , Camundongos , Estrutura Molecular , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Própole/metabolismo , Espécies Reativas de Oxigênio , Espectrometria de Massas por Ionização por Electrospray , Células Vero
2.
BMC Neurosci ; 15: 132, 2014 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-25552352

RESUMO

BACKGROUND: Assembly and disassembly of microtubules (MTs) is critical for neurite outgrowth and differentiation. Evidence suggests that nerve growth factor (NGF) induces neurite outgrowth from PC12 cells by activating the receptor tyrosine kinase, TrkA. G protein-coupled receptors (GPCRs) as well as heterotrimeric G proteins are also involved in regulating neurite outgrowth. However, the possible connection between these pathways and how they might ultimately converge to regulate the assembly and organization of MTs during neurite outgrowth is not well understood. RESULTS: Here, we report that Gßγ, an important component of the GPCR pathway, is critical for NGF-induced neuronal differentiation of PC12 cells. We have found that NGF promoted the interaction of Gßγ with MTs and stimulated MT assembly. While Gßγ-sequestering peptide GRK2i inhibited neurite formation, disrupted MTs, and induced neurite damage, the Gßγ activator mSIRK stimulated neurite outgrowth, which indicates the involvement of Gßγ in this process. Because we have shown earlier that prenylation and subsequent methylation/demethylation of γ subunits are required for the Gßγ-MTs interaction in vitro, small-molecule inhibitors (L-28 and L-23) targeting prenylated methylated protein methyl esterase (PMPMEase) were tested in the current study. We found that these inhibitors disrupted Gßγ and ΜΤ organization and affected cellular morphology and neurite outgrowth. In further support of a role of Gßγ-MT interaction in neuronal differentiation, it was observed that overexpression of Gßγ in PC12 cells induced neurite outgrowth in the absence of added NGF. Moreover, overexpressed Gßγ exhibited a pattern of association with MTs similar to that observed in NGF-differentiated cells. CONCLUSIONS: Altogether, our results demonstrate that ßγ subunit of heterotrimeric G proteins play a critical role in neurite outgrowth and differentiation by interacting with MTs and modulating MT rearrangement.


Assuntos
Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Microtúbulos/metabolismo , Fator de Crescimento Neural/metabolismo , Neuritos/fisiologia , Animais , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Hidrolases de Éster Carboxílico/metabolismo , Crescimento Celular , Células Cultivadas , Cerebelo/citologia , Cerebelo/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Células PC12 , Ratos , Ratos Sprague-Dawley , Tubulina (Proteína)/metabolismo
3.
Cell Motil Cytoskeleton ; 64(12): 936-50, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17705289

RESUMO

The betagamma subunit of G proteins (Gbetagamma) is known to transfer signals from cell surface receptors to intracellular effector molecules. Recent results suggest that Gbetagamma also interacts with microtubules and is involved in the regulation of the mitotic spindle. In the current study, the anti-microtubular drug nocodazole was employed to investigate the mechanism by which Gbetagamma interacts with tubulin and its possible implications in microtubule assembly in cultured PC12 cells. Nocodazole-induced depolymerization of microtubules drastically inhibited the interaction between Gbetagamma and tubulin. Gbetagamma was preferentially bound to microtubules and treatment with nocodazole suggested that the dissociation of Gbetagamma from microtubules is an early step in the depolymerization process. When microtubules were allowed to recover after removal of nocodazole, the tubulin-Gbetagamma interaction was restored. Unlike Gbetagamma, however, the interaction between tubulin and the alpha subunit of the Gs protein (Gsalpha) was not inhibited by nocodazole, indicating that the inhibition of tubulin-Gbetagamma interactions during microtubule depolymerization is selective. We found that Gbetagamma also interacts with gamma-tubulin, colocalizes with gamma-tubulin in centrosomes, and co-sediments in centrosomal fractions. The interaction between Gbetagamma and gamma-tubulin was unaffected by nocodazole, suggesting that the Gbetagamma-gamma-tubulin interaction is not dependent on assembled microtubules. Taken together, our results suggest that Gbetagamma may play an important and definitive role in microtubule assembly and/or stability. We propose that betagamma-microtubule interaction is an important step for G protein-mediated cell activation. These results may also provide new insights into the mechanism of action of anti-microtubule drugs.


Assuntos
Subunidades beta da Proteína de Ligação ao GTP/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Microtúbulos/metabolismo , Tubulina (Proteína)/metabolismo , Animais , Centrômero/química , Centrômero/metabolismo , Subunidades beta da Proteína de Ligação ao GTP/análise , Subunidades beta da Proteína de Ligação ao GTP/efeitos dos fármacos , Subunidades gama da Proteína de Ligação ao GTP/análise , Subunidades gama da Proteína de Ligação ao GTP/efeitos dos fármacos , Camundongos , Microtúbulos/química , Microtúbulos/efeitos dos fármacos , Células NIH 3T3 , Nocodazol/farmacologia , Células PC12 , Ratos , Tubulina (Proteína)/análise , Moduladores de Tubulina/farmacologia
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