RESUMO
INTRODUCTION: The pulmonary inflammatory response results from exposure to injurious factors and is associated with oxidative stress, which intensifies the pathological reaction. In this context, limonene, a monoterpene found in citrus fruits, can be a therapeutic alternative for the treatment of this pathology, as it presents known anti-inflammatory and antioxidant actions. OBJECTIVE: The purpose of this article is to provide an overview of the anti-inflammatory activity of limonene and its capacity to prevent and control respiratory system injuries. SEARCH STRATEGY: A comprehensive literature search of the Cochrane, Scopus, MEDLINE-PubMed, Web of Science, and Lilacs databases was performed using the keywords: "limonene", "lung", "pulmonary", "airway", "trachea", "lung injury", "respiratory system", "respiratory tract diseases". SELECTION CRITERIA: Studies on the use of limonene in disorders of the respiratory system, published until August 2019, were included. Those that did not use limonene alone or treated lesions in different systems other than the respiratory system, without targeting its anti-inflammatory action were excluded. In addition, review articles, meta-analyses, abstracts, conference papers, editorials/letters and case reports were also excluded. RESULTS: Of the 561 articles found, 64 were in the Cochrane database, 235 in Scopus, 99 in Web of science, 150 in PubMed and 13 in Lilacs. After completing the systematic steps, 25 articles were selected for full reading, after which 7 papers remained in the review. An article was added after a manual literature search, resulting in a total of 8 papers. There was a high level of agreement on inclusion/exclusion among the researchers who examined the papers (Kappa index > 88%). CONCLUSION: Limonene has effective anti-inflammatory activity in both preventing and controlling respiratory system injuries.
Assuntos
Anti-Inflamatórios , Sistema Respiratório , Anti-Inflamatórios/farmacologia , Limoneno/química , Limoneno/farmacologia , Metanálise como Assunto , Monoterpenos , Estresse Oxidativo , Terpenos/química , Terpenos/farmacologiaRESUMO
The SCF (Skp1-Cul1-F-box) complex is one of the several E3 ligase enzymes and it catalyzes protein ubiquitination and degradation by the 26S proteasome. Rbx1 is a member of the SCF complex in humans and HRT1 is its yeast orthologue. A cDNA encoding a Schistosoma mansoni Rbx1 homolog was cloned and functionally characterized. Heterologous functional complementation in yeast showed that the worm SmRbx gene was able to complement the HRT1yeast null mutation. Gene deletion constructs for N- and C-termini truncated proteins were used to transform hrt1(-) yeast mutant strains, allowing us to observe that regions reported to be involved in the interaction with cullin1 (Cul1) were essential for SmRbx function. Yeast two-hybrid assays using SmRbx and yeast Cul1 confirmed that SmRbx, but not the mutant SmRbxDelta24N, lacking the N-terminus of the protein, was capable of interacting with Cul1. These results suggest that SmRbx protein is involved in the SCF complex formation.
Assuntos
Proteínas de Helminto/genética , Schistosoma mansoni/genética , Ubiquitina/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Transporte/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Culina/genética , Proteínas Culina/metabolismo , DNA Complementar/química , DNA de Helmintos/química , Etiquetas de Sequências Expressas , Feminino , Teste de Complementação Genética , Vetores Genéticos , Proteínas de Helminto/química , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Ligases SKP Culina F-Box , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Schistosoma mansoni/metabolismoRESUMO
In a previous study, the Schistosoma mansoni Rho1 protein was able to complement Rho1 null mutant Saccharomyces cerevisiae cells at restrictive temperatures and under osmotic stress (low calcium concentration) better than the human homologue (RhoA). It is known that under osmotic stress, the S. cerevisiae Rho1 triggers two distinct pathways: activation of the membrane 1,3-beta-glucan synthase enzymatic complex and activation of the protein kinase C1 signal transduction pathway, promoting the transcription of response genes. In the present work the SmRho1 protein and its mutants smrho1E97P, smrho1L101T, and smrho1E97P, L101T were used to try to clarify the basis for the differential complementation of Rho1 knockout yeast strain by the human and S. mansoni genes. Experiments of functional complementation in the presence of caffeine and in the presence of the osmotic regulator sorbitol were conducted. SmRho1 and its mutants showed a differential complementation of the yeast cells in the presence of caffeine, since smrho1E97P and smrho1E97P, L101T mutants showed a delay in the growth when compared to the yeast complemented with the wild type SmRho1. However, in the presence of sorbitol and caffeine the wild type SmRho1 and mutants showed a similar complementation phenotype, as they allowed yeast growth in all caffeine concentrations tested.
Assuntos
Animais , Humanos , Cafeína/farmacologia , Proteína Quinase C/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Schistosoma mansoni/genética , Proteínas rho de Ligação ao GTP/genética , Genes de Helmintos , Mutação , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Schistosoma mansoni/metabolismo , Transdução de Sinais/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
In a previous study, the Schistosoma mansoni Rho1 protein was able to complement Rho1 null mutant Saccharomyces cerevisiae cells at restrictive temperatures and under osmotic stress (low calcium concentration) better than the human homologue (RhoA). It is known that under osmotic stress, the S. cerevisiae Rho1 triggers two distinct pathways: activation of the membrane 1,3-beta-glucan synthase enzymatic complex and activation of the protein kinase C1 signal transduction pathway, promoting the transcription of response genes. In the present work the SmRho1 protein and its mutants smrho1E97P, smrho1L101T, and smrho1E97P, L101T were used to try to clarify the basis for the differential complementation of Rho1 knockout yeast strain by the human and S. mansoni genes. Experiments of functional complementation in the presence of caffeine and in the presence of the osmotic regulator sorbitol were conducted. SmRho1 and its mutants showed a differential complementation of the yeast cells in the presence of caffeine, since smrho1E97P and smrho1E97P, L101T mutants showed a delay in the growth when compared to the yeast complemented with the wild type SmRho1. However, in the presence of sorbitol and caffeine the wild type SmRho1 and mutants showed a similar complementation phenotype, as they allowed yeast growth in all caffeine concentrations tested.
Assuntos
Cafeína/farmacologia , Proteína Quinase C/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Schistosoma mansoni/genética , Proteínas rho de Ligação ao GTP/genética , Animais , Genes de Helmintos , Humanos , Mutação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Schistosoma mansoni/metabolismo , Transdução de Sinais/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
The human nuclear protein RbAp48 is a member of the tryptophan/aspartate (WD) repeat family, which binds to the retinoblastoma (Rb) protein. It also corresponds to the smallest subunit of the chromatin assembly factor and is able to bind to the helix 1 of histone H4, taking it to the DNA in replication. A cDNA homologous to the human gene RbAp48 was isolated from a Schistosoma mansoni adult worm library and named SmRbAp48. The full length sequence of SmRbAp48 cDNA is 1036 bp long, encoding a protein of 308 amino acids. The transcript of SmRbAp48 was detected in egg, cercariae and schistosomulum stages. The protein shows 84% similarity with the human RbAp48, possessing four WD repeats on its C-terminus. A hypothetical tridimensional structure for the SmRbAp48 C-terminal domain was constructed by computational molecular modeling using the b-subunit of the G protein as a model. To further verify a possible interaction between SmRbAp48 and S. mansoni histone H4, the histone H4 gene was amplified from adult worm genomic DNA using degenerated primers. The gene fragment of SmH4 is 294 bp long, encoding a protein of 98 amino acids which is 100% identical to histone H4 from Drosophila melanogaster.
Assuntos
Proteínas de Transporte/genética , Proteínas de Helminto/química , Histonas/genética , Proteínas Nucleares/genética , Schistosoma mansoni/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Expressão Gênica , Biblioteca Gênica , Genes de Helmintos/genética , Proteínas Heterotriméricas de Ligação ao GTP , Humanos , Estágios do Ciclo de Vida , Dados de Sequência Molecular , Proteína 4 de Ligação ao Retinoblastoma , Schistosoma mansoni/crescimento & desenvolvimentoRESUMO
The human nuclear protein RbAp48 is a member of the tryptophan/aspartate (WD) repeat family, which binds to the retinoblastoma (Rb) protein. It also corresponds to the smallest subunit of the chromatin assembly factor and is able to bind to the helix 1 of histone H4, taking it to the DNA in replication. A cDNA homologous to the human gene RbAp48 was isolated from a Schistosoma mansoni adult worm library and named SmRbAp48. The full length sequence of SmRbAp48 cDNA is 1036 bp long, encoding a protein of 308 amino acids. The transcript of SmRbAp48 was detected in egg, cercariae and schistosomulum stages. The protein shows 84% similarity with the human RbAp48, possessing four WD repeats on its C-terminus. A hypothetical tridimensional structure for the SmRbAp48 C-terminal domain was constructed by computational molecular modeling using the b-subunit of the G protein as a model. To further verify a possible interaction between SmRbAp48 and S. mansoni histone H4, the histone H4 gene was amplified from adult worm genomic DNA using degenerated primers. The gene fragment of SmH4 is 294 bp long, encoding a protein of 98 amino acids which is 100% identical to histone H4 from Drosophila melanogaster
