RESUMEN

NK-lysins are antimicrobial peptides (AMPs) that participate in the innate immune response and also have several pivotal roles in various biological processes. Such multifunctionality is commonly found among intrinsically disordered proteins. However, NK-lysins have never been systematically analyzed for intrinsic disorder. To fill this gap, the amino acid sequences of NK-lysins from various species were collected from UniProt and used for the comprehensive computational analysis to evaluate the propensity of these proteins for intrinsic disorder and to investigate the potential roles of disordered regions in NK-lysin functions. We analyzed abundance and peculiarities of intrinsic disorder distribution in all-known NK-lysins and showed that many NK-lysins are expected to have substantial levels of intrinsic disorder. Curiously, high level of intrinsic disorder was also found even in two proteins with known 3D-strucutres (NK-lysin from pig and human granulysin). Many of the identified disordered regions can be involved in protein-protein interactions. In fact, NK-lysins are shown to contain three to eight molecular recognition features; i.e. short structure-prone segments which are located within the long disordered regions and have a potential to undergo a disorder-to-order transition upon binding to a partner. Furthermore, these disordered regions are expected to have several sites of various posttranslational modifications. Our study shows that NK-lysins, which are AMPs with a set of prominent roles in the innate immune response, are expected to abundantly possess intrinsically disordered regions that might be related to multifunctionality of these proteins in the signal transduction pathways controlling the host response to pathogenic agents.

Asunto(s)

Algoritmos , Antiinfecciosos/química , Antígenos de Diferenciación de Linfocitos T/química , Proteolípidos/química , Secuencia de Aminoácidos , Animales , Antiinfecciosos/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Biología Computacional , Humanos , Modelos Moleculares , Familia de Multigenes , Conformación Proteica , Proteolípidos/metabolismo , Homología de Secuencia de Aminoácido , Porcinos

RESUMEN

This study was performed to identify the expression patterns of the cathelicidin genes in a local chicken breed and to evaluate the antimicrobial activities of the cathelicidin peptides against pathogenic bacteria. This analysis revealed that the coding regions of CATH-1, -2, and -3 genes contain 447 bp, 465 bp, and 456 bp, respectively, and encode proteins of 148, 154, 151 amino acids, respectively. The complete amino acid sequences of the cathelicidin peptides are similar to those found in Meleagris gallopavo, Phasianus colchicus, and Coturnix coturnix, and show high sequence identity to their Columba livia and Anas platyrhynchos counterparts. In contrast, these avian peptides shared a very low sequence identity with the mammalian cathelicidins. The analysis further revealed that the cathelicidin genes are expressed in various organ and tissues. We also show that the CATH peptides 1, 2, 3 and their amide-modified structures possess potent antimicrobial activities against both Gram-positive and Gram-negative pathogens, with these bacteria being affected to different extents. The antimicrobial activities of the peptides are slightly lower than those of their amide analogs. Computational analysis revealed that pre-pro-cathelicidins are hybrid proteins that contain ordered domains and functional intrinsically disordered regions. Furthermore, high structural and sequence variability of mature cathelicidins is a strong indication of their rather disordered nature. It is likely that intrinsic disorder is needed for the multifarious functionality of these antimicrobial peptides. Our analyses indicated that cathelicidin peptides require further study to better understand their full potentials in the treatment of diseases in both humans and animals. The data obtained for synthetic avian peptides will help elucidating of their potential applications in the pharmaceutical industry.

Asunto(s)

Antiinfecciosos/metabolismo , Catelicidinas/metabolismo , Pollos/inmunología , Desinfectantes/metabolismo , Amidas/química , Animales , Antiinfecciosos/química , Biodiversidad , Catelicidinas/química , Catelicidinas/genética , Biología Computacional , Desinfectantes/química , Evolución Molecular , Humanos , Mamíferos , Filogenia , Alineación de Secuencia , Homología Estructural de Proteína , Transcriptoma

RESUMEN

INTRODUCTION: The historical use of black cumin seed (Nigella sativa) dates back centuries, being embedded in Arabian culture and having a long history of unsurpassed medicinal value with versatility to treat a wide range of ailments. Thymoquinone (TQ) is now known to be the primary active constituent of black cumin seed oil (BCS oil) responsible for its medicinal effects and also showing promise for treatment of cancer. MATERIAL AND METHODS: In the current study, we have studied the effects of TQ and BCS oil on tumor markers (MDA, LDH, ALP and AST), histopathological alterations and the regulation of several genes (Brca1, Brca2, Id-1 and P53 mutation) related to breast cancer in female rats induced by 7,12-dimethylbenz[a]anthracene (DMBA) treatment. Rats received a single dose (65 mg/kg b.w.) of DMBA via an intragastric tube to induce breast cancer. Animals that received DMBA were treated orally with 1, 5, 10 mg/kg of TQ or BCS oil via an intragastric tube three times per week for 4 months. RESULTS: We found that TQ and then BCS reduced the rate of tumor markers (levels of MDA and LDH as well as ALP and AST activities), inhibited the histopathological alterations and decreased the expression of the Brca1, Brca2, Id-1 and P53 mutations in mammary tissues of female rats induced by DMBA treatment. CONCLUSIONS: The results suggest that TQ and BCS oil exert a protective effect against breast carcinogens. The antioxidant property of TQ and BCS oil is mediated by their actions and investigating other underlying mechanisms merits further studies.