Protein-protein interactions of the nicotinamide/nicotinate mononucleotide adenylyltransferase of Leishmania braziliensis

Ortiz-Joya, Lesly Johanna; Contreras-Rodríguez, Luis Ernesto; Ramírez-Hernández, María Helena

doi:10.1590/0074-02760180506

Cited by 8 publications

(5 citation statements)

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“…Para la contención de diversas especies reactivas en el proceso de infección, el parásito depende de isoenzimas mitocondriales y citoplasmáticas de la TXNPx, las cuales, a su vez, dependen del NADPH para catalizar sus reacciones. Estudios previos han reportado en L. braziliensis la interacción molecular entre proteínas propias de los sistemas antioxidantes con aquellas involucradas en la síntesis del NAD, como la NMNAT [12]. Dicha evidencia se confirmó en el presente estudio (Figura 10), en el Figura 10.…”

Section: Discussionunclassified

“…La TXNPx es indispensable para la supervivencia del parásito puesto que se encarga de la destoxificación primaria de H 2 O 2 , una amplia gama de hidroperóxidos orgánicos y, en algunos casos, ONOO -, un componente esencial del principal sistema de captación enzimática para ROS y RNI en tripanosomátidos [15]. La acción combinada de la TXNPx con enzimas antioxidantes es crucial para el mantenimiento de una baja concentración de H 2 O 2 , regulando el estrés oxidativo y nitrosativo a través del desplazamiento de equivalentes reductores desde el NADPH hacia hidroperóxidos y peroxinitritos [12].…”

Section: Introductionunclassified

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Identificación de una triparedoxina peroxidasa citoplasmática en Leishmania braziliensis

et al. 2021

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Los sistemas de defensa anti-oxidante utilizados por el parásito intracelular Leishmania braziliensis durante el proceso de infección permiten eliminar especies reactivas de oxígeno y nitrógeno a expensas de equivalentes reductores derivados de la tripanotiona, evitando daños celulares del patógeno. Con el objetivo de identificar potenciales blancos moleculares para el desarrollo de fármacos contra este parásito, se realizó la detección de la enzima triparedoxina peroxidasa citoplasmática de L. braziliensis (LbTXNPxII), la cual es esencial para disminuir concentraciones tóxicas de peróxido de hidrógeno en el contexto de infección. Para esto se generaron anticuerpos policlonales en modelo aviar, partiendo de la clonación, expresión y purificación de la proteína recombinante 6xHis-SUMO-LbTXNPxII (37kDa) en el sistema heterólogo Escherichia coli. La proteína purificada se utilizó como antígeno para la producción de anticuerpos IgY, cuya implementación en estudios in situ permitió detectar y localizar la enzima LbTXNPxII endógena (22kDa) en el citoplasma de promastigotes fijados y verificar su interacción molecular con la nicotinamida/nicotinato mononucleótido adenilil transferasa, enzima involucrada en la síntesis del NAD. De este modo, se reporta el desarrollo de una herramienta bioquímica para la identificación y estudio de la enzima LbTXNPxII y su participación en vías del metabolismo energético y de defensa anti-oxidante.

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Section: Discussionunclassified

Section: Introductionunclassified

Identificación de una triparedoxina peroxidasa citoplasmática en Leishmania braziliensis

et al. 2021

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“…On the other hand, nicotinamide adenine dinucleotide (NAD) plays a central role in energy metabolism and integrates cell metabolism with signaling and gene expression [ 23 ]. NAD biosynthesis is dependent on nicotinamide/nicotinate single-nucleotide adenylate transferase [ 24 ]. Therefore, high-risk patients may benefit from metabolic therapy, while low-risk patients may benefit from nonmetabolism-targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

Tang

Zhou

2020

Mediators of Inflammation

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Background. Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that emanates from the lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and from other pharyngeal cancers. The availability of high-throughput expression data has made it possible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients. Method. In this study, we used RNA sequencing (RNA-seq) data from the cancer genome atlas (TCGA), with validation in the GEO dataset to profile the metabolic microenvironment and define potential biomarkers for metabolic therapy. Results. We extracted data for 529 patients and 327 metabolic genes (198 upregulated and 129 downregulated genes) in the TCGA database. Carbonic anhydrase 9 (CA9) and CA6 had the largest logFCs in the upregulated and downregulated genes, respectively. Our Cox regression model data showed 51 prognostic-related genes with lysocardiolipin acyltransferase 1 (LCLAT1) and choline dehydrogenase (CHDH) being associated with the highest risk ( HR = 1.144 , 95% CI = 1.044 ~ 1.251 ) and the lowest risk ( HR = 0.580 , 95% CI = 0.400 ~ 0.839 ) in HNSCC, respectively. We next used the ROC curve to evaluate whether the differentially expressed metabolic-related genes could serve as early predictors of HNSCC. The findings showed an AUC of 0.745 and 0.618 in the TCGA and GEO analysis, respectively. Besides, the ability for the genes to predict clinicopathological HNSCC status was analyzed and the data showed that the AUC for age, gender, grade, stage, T, M, and N was 0.520, 0.495, 0.568, 0.606, 0.577, 0.476, and 0.673, respectively, in the TCGA dataset. On the other hand, the AUC for age, gender, stage, T, M, N, smoking, and HPV16-pos was 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519, and 0.397, respectively, in the GEO dataset. Conclusion. Taken together, our study unearths a novel metabolic gene signature for the prediction of HNSCC prognosis based on the TCGA dataset. Our signature might point out the metabolic microenvironment disorders and provides potential treatment targets and prognostic biomarkers.

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“…Nicotinamide adenine dinucleotide (NAD) plays a central role in energy metabolism and integrates cell metabolism with signaling and gene expression 23 . NAD biosynthesis is dependent on nicotinamide/nicotinate single nucleotide adenylate transferase 24 . From this perspective, high-risk patients may bene t from metabolic therapy, while low-risk patients may bene t from non-metabolic therapy.…”

Section: Discussionmentioning

confidence: 99%

Identification of a metabolic signature genes predicting overall survival for Head and neck squamous cell carcinoma

Wu¹,

Zhou²

2020

Preprint

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Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a common head and neck malignancy that originates from lips, mouth, paranasal sinuses, oropharynx, larynx, nasopharynx, and other pharyngeal cancers. Since high-throughput expression data is now available, it is feasible to use global gene expression data to analyze the relationship between metabolic-related gene expression and clinical outcomes in HNSCC patients. Method: In this study, we used RNA sequencing (RNA-seq) data from cancer genomic maps (TCGA) and validated in the GEO dataset to shine the dysfunctional metabolic microenvironment and given potential biomarkers for metabolic therapy.Results: TCGA database contained 529 patients and 327 metabolic genes (198 upregulated and the largest logFC is CA9; 129 downregulated and the largest logFC is CA6. Cox regression model found 51 prognosis‐related genes and we found the most high-risk gene was LCLAT1 (HR=1.144, 95% CI=1.044~1.251); the most low-risk gene was CHDH (HR=0.580, 95% CI=0.400~0.839). We next study whether metabolic-related genes patterns could serve as an early predictor of incidence of HNSCC by ROC curve and the model demonstrated an AUC of 0.745 in TCGA and 0.618 in GEO. Meanwhile, the predictor of clinicopathological in HNSCC was also analyzed and we found the AUC for age, gender, grade, stage, T, M and N were 0.520, 0.495, 0.568, 0.606, 0.577, 0.476 and 0.673, respectively in TCGA and the AUC for age, gender, stage, T, M, N, smoking and HPV16-pos were 0.599, 0.531, 0.622, 0.606, 0.616, 0.550, 0.614, 0.519 and 0.397 respectively in GEO.Conclusion: Our research found a novel metabolic signature gene for HNSCC prognosis prediction based on the TCGA dataset. Our signatures may reflect metabolic microenvironment disorders and provide useful biomarkers for metabolic therapy and response treatment prediction.

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Protein-protein interactions of the nicotinamide/nicotinate mononucleotide adenylyltransferase of Leishmania braziliensis

Cited by 8 publications

References 35 publications

Identificación de una triparedoxina peroxidasa citoplasmática en Leishmania braziliensis

Identificación de una triparedoxina peroxidasa citoplasmática en Leishmania braziliensis

A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

Identification of a metabolic signature genes predicting overall survival for Head and neck squamous cell carcinoma

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