RESUMO
Tetramethylpyrazine (TMP), a biologically active ingredient first extracted from the Chinese medicinal plant Ligusticum wallichii Franchat., has athero-protective activity, yet the particular mechanisms have not been completely explored. The present study was designed to investigate the effect of TMP and its possible mechanisms in RAW264.7 macrophages and apolipoprotein E-deficient (ApoE-/-) mice. TMP treatment markedly increased the cholesterol efflux and inhibited oxidized low-density lipoprotein (ox-LDL) uptake, thus, ameliorating lipid accumulation in macrophages. In addition, TMP significantly increased the protein and mRNA expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), while suppressing the protein and mRNA expression of class A scavenger receptor (SR-A) and the cluster of differentiation 36 (CD36). Moreover, the effects of TMP on the upregulation of the expression of ABCA1 and ABCG1, the downregulation of the expression of CD36 and SR-A, the increase of cholesterol efflux and the decrease of lipid accumulation as well as the uptake of ox-LDL were mediated by the inactivation of PI3K/Akt and p38 MAPK. Furthermore, TMP upregulated the protein stability of ABCA1 without affecting ABCG1. Accordingly, TMP regulated the expression of SR-A, CD36, ABCA1 and ABCG1 in aortas of ApoE-/- mice, which resembled the findings observed in macrophages. TMP was also capable of delaying the progression of atherosclerosis in ApoE-/- mice. These findings revealed that TMP downregulates scavenger receptors and upregulates ATP-binding cassette transporters via PI3K/Akt and p38 MAPK signaling, thus suppressing lipid accumulation in macrophages.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Antígenos CD36/genética , Pirazinas/administração & dosagem , Receptores Depuradores Classe A/genética , Animais , Apolipoproteínas E/genética , Colesterol/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Ligusticum/química , Metabolismo dos Lipídeos/genética , Lipoproteínas LDL/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Células RAW 264.7RESUMO
Aromatic L-amino acid decarboxylases (AADCs) are key enzymes operating at the interface between primary and secondary metabolism. The Arabidopsis thaliana genome contains two genes, At2g20340 and At4g28680, encoding pyridoxal 5'-phosphate-dependent AADCs with high homology to the recently identified Petunia hybrida phenylacetaldehyde synthase involved in floral scent production. The At4g28680 gene product was recently biochemically characterized as an L-tyrosine decarboxylase (AtTYDC), whereas the function of the other gene product remains unknown. The biochemical and functional characterization of the At2g20340 gene product revealed that it is an aromatic aldehyde synthase (AtAAS), which catalyzes the conversion of phenylalanine and 3,4-dihydroxy-L-phenylalanine to phenylacetaldehyde and dopaldehyde, respectively. AtAAS knock-down and transgenic AtAAS RNA interference (RNAi) lines show significant reduction in phenylacetaldehyde levels and an increase in phenylalanine, indicating that AtAAS is responsible for phenylacetaldehyde formation in planta. In A. thaliana ecotype Columbia (Col-0), AtAAS expression was highest in leaves, and was induced by methyl jasmonate treatment and wounding. Pieris rapae larvae feeding on Col-0 leaves resulted in increased phenylacetaldehyde emission, suggesting that the emitted aldehyde has a defensive activity against attacking herbivores. In the ecotypes Sei-0 and Di-G, which emit phenylacetaldehyde as a predominant flower volatile, the highest expression of AtAAS was found in flowers and RNAi AtAAS silencing led to a reduction of phenylacetaldehyde formation in this organ. In contrast to ecotype Col-0, no phenylacetaldehyde accumulation was observed in Sei-0 upon wounding, suggesting that AtAAS and subsequently phenylacetaldehyde contribute to pollinator attraction in this ecotype.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Descarboxilases de Aminoácido-L-Aromático/metabolismo , Folhas de Planta/metabolismo , Tirosina Descarboxilase/metabolismo , Acetaldeído/análogos & derivados , Acetaldeído/metabolismo , Acetatos/farmacologia , Animais , Arabidopsis/efeitos dos fármacos , Arabidopsis/parasitologia , Proteínas de Arabidopsis/genética , Descarboxilases de Aminoácido-L-Aromático/genética , Ciclopentanos/farmacologia , Comportamento Alimentar , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Insetos/patogenicidade , Larva/patogenicidade , Odorantes , Oxilipinas/farmacologia , Filogenia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/enzimologia , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/enzimologia , Plantas Geneticamente Modificadas/parasitologia , Pólen/genética , Pólen/metabolismo , Interferência de RNA , Homologia de Sequência de Aminoácidos , Tirosina Descarboxilase/genética , Compostos Orgânicos Voláteis/metabolismo , VolatilizaçãoRESUMO
A high-G+C-content, Gram-positive bacterium, strain D10(T), was isolated from the root of Oroxylum indicum, a Chinese medicinal plant. Based on 16S rRNA gene sequence analysis, strain D10(T) was a member of the genus Pseudonocardia and was most closely related, albeit loosely, to Pseudonocardia halophobica. Morphological and chemotaxonomic characteristics support the affiliation of strain D10(T) to the genus Pseudonocardia. Results of DNA-DNA hybridization and physiological and biochemical tests allowed genotypic and phenotypic differentiation of strain D10(T) from related Pseudonocardia species. Strain D10(T) (=CGMCC 4.3143(T)=DSM 44984(T)) therefore represents a novel species, for which the name Pseudonocardia oroxyli sp. nov. is proposed.