Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1

The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity. © 2013 Elsevier GmbH. All rights reserved.

Platelet-Rich Plasma And Chronic Wounds: Remaining Fibronectin May Influence Matrix Remodeling And Regeneration Success

Background: Platelet-rich plasma has been largely used as a therapeutic option for the treatment of chronic wounds of different etiologies. The enhanced regeneration observed after the use of platelet-rich plasma has been systematically attributed to the growth factors that are present inside platelets' granules. Aim: We hypothesize that the remaining plasma and platelet-bound fibronectin may act as a further bioactive protein in platelet-rich plasma preparations. Methods: Recent reports were analyzed and presented as direct evidences of this hypotheses. Results: Fibronectin may directly influence the extracellular matrix remodeling during wound repair. This effect is probably through matrix metalloproteinase expression, thus exerting an extra effect on chronic wound regeneration. Conclusions: Physicians should be well aware of the possible fibronectin-induced effects in their future endeavors with PRP in chronic wound treatment. © 2013 International Society for Cellular Therapy.

Contribuição eletrostática e não eletrostática na interação de peptídeos líticos com membranas modelo

Pós-graduação em Biofísica Molecular - IBILCE

Contribuição ao estudo bioquímico de polpa de híbridos da cultivar maracujá amarelo azedo (Passiflora edulis f. flavicarpa Degener): enzimas e compostos bioativos

Pós-graduação em Biotecnologia - IQ

Caracterização bioquímica e centesimal das espécies Astrocaryum vulgare Mart. (tucumã) e Endopleura uchi (Huber) Cuatrec. (uxi) nativas da região Amazônica

Pós-graduação em Biotecnologia - IQ

Influência das condições de cultivo e métodos de extração na produção de metabólitos antioxidantes por fungos isolados do litoral paulista

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Uso do curativo bio-ativo em pacientes com feridas de origem multifatorial

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Potencial imunogênico dos curativos bioativos: aspectos imunhematológicos e leucoplaquetários

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização química, microbiológica e farmacognóstica da polpa de coquinho-azedo (Butia capitata (Mart) Becc) produzida em Arinos-MG

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O emprego da metodologia de superfície de resposta no desenvolvimento de um novo produto simbiótico, fermentado com Enterococcus faecium CRL 183 e Lactobacillus helveticus ssp jugurti 416, à base de extratos aquosos de soja e de Yacon (Smallanthus sonchifolius)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da composição química de óleos extraídos de sementes de abóboras (Cucurbita sp)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização e propriedades funcionais de óleos extraídos de castanhas e nozes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Propriedades físico-químicas de abacate submetido à secagem convectiva e desidratação osmótica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização dos frutos e dos óleos extraídos da polpa e amêndoa de guariroba (Syagrus oleracea), Jerivá (Syagrus romanzoffiana) e macaúba (Acromia aculeata)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Síntese de sucroésteres derivados de ácidos piridínicos (ácido nicotínico, isonicotínico e pícolínico) e avaliação de suas atividades antimicrobianas

Pós-graduação em Engenharia e Ciência de Alimentos - IBILCE