Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabete...

Autores
Hernández Bustamante, Israel; Santander Plantamura, Yanina Alejandra; Mata Espinosa, Dulce; Reyes Chaparro, Andrés; Bini, Estela Isabel; Torre Villalvazo, Iván; Tovar, Armando R.; Barrios Payan, Jorge; Marquina Castillo, Brenda; Hernández Pando, Rogelio; Carranza, Maria Andrea
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Metabolic syndrome is considered the precursor of type 2 diabetes mellitus. Tuberculosis is a leading infection that constitutes a global threat remaining a major cause of morbi-mortality in developing countries. People with type 2 diabetes mellitus are more likely to suffer from infection with Mycobacterium tuberculosis. For both type 2 diabetes mellitus and tuberculosis, there is pulmonary production of anti-inflammatory glucocorticoids mediated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal hormone dehydroepiandrosterone (DHEA) counteracts the glucocorticoid effects of cytokine production due to the inhibition of 11β-HSD1. Late advanced tuberculosis has been associated with the suppression of the Th1 response, evidenced by a high ratio of cortisol/DHEA. In a murine model of metabolic syndrome, we determined whether DHEA treatment modifies the pro-inflammatory cytokines due to the inhibition of the 11β-HSD1 expression. Since macrophages express 11β-HSD1, our second goal was incubating them with DHEA and Mycobacterium tuberculosis to show that the microbicide effect was increased by DHEA. Enoyl-acyl carrier protein reductase (InhA) is an essential enzyme of Mycobacterium tuberculosis involved in the mycolic acid synthesis. Because 11β-HSD1 and InhA are members of a short-chain dehydrogenase/reductase family of enzymes, we hypothesize that DHEA could be an antagonist of InhA. Our results demonstrate that DHEA has a direct microbicide effect against Mycobacterium tuberculosis; this effect was supported by in silico docking analysis and the molecular dynamic simulation studies between DHEA and InhA. Thus, DHEA increases the production of pro-inflammatory cytokines in the lung, inactivates GC by 11β-HSD1, and inhibits mycobacterial InhA. The multiple functions of DHEA suggest that this hormone or its synthetic analogs could be an efficient co-adjuvant for tuberculosis treatment.
Fil: Hernández Bustamante, Israel. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Santander Plantamura, Yanina Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Reyes Chaparro, Andrés. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Toxicología; México
Fil: Bini, Estela Isabel. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Torre Villalvazo, Iván. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Tovar, Armando R.. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Barrios Payan, Jorge. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Marquina Castillo, Brenda. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Carranza, Maria Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
11Β-HYDROXYSTEROID DEHYDROGENASE
DEHYDROEPIANDROSTERONE
GLUCOCORTICOID
INFLAMMATION
INHA
LUNG
TUBERCULOSIS
TYPE 2 DIABETES MELLITUS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/225064
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidityHernández Bustamante, IsraelSantander Plantamura, Yanina AlejandraMata Espinosa, DulceReyes Chaparro, AndrésBini, Estela IsabelTorre Villalvazo, IvánTovar, Armando R.Barrios Payan, JorgeMarquina Castillo, BrendaHernández Pando, RogelioCarranza, Maria Andrea11Β-HYDROXYSTEROID DEHYDROGENASEDEHYDROEPIANDROSTERONEGLUCOCORTICOIDINFLAMMATIONINHALUNGTUBERCULOSISTYPE 2 DIABETES MELLITUShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Metabolic syndrome is considered the precursor of type 2 diabetes mellitus. Tuberculosis is a leading infection that constitutes a global threat remaining a major cause of morbi-mortality in developing countries. People with type 2 diabetes mellitus are more likely to suffer from infection with Mycobacterium tuberculosis. For both type 2 diabetes mellitus and tuberculosis, there is pulmonary production of anti-inflammatory glucocorticoids mediated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal hormone dehydroepiandrosterone (DHEA) counteracts the glucocorticoid effects of cytokine production due to the inhibition of 11β-HSD1. Late advanced tuberculosis has been associated with the suppression of the Th1 response, evidenced by a high ratio of cortisol/DHEA. In a murine model of metabolic syndrome, we determined whether DHEA treatment modifies the pro-inflammatory cytokines due to the inhibition of the 11β-HSD1 expression. Since macrophages express 11β-HSD1, our second goal was incubating them with DHEA and Mycobacterium tuberculosis to show that the microbicide effect was increased by DHEA. Enoyl-acyl carrier protein reductase (InhA) is an essential enzyme of Mycobacterium tuberculosis involved in the mycolic acid synthesis. Because 11β-HSD1 and InhA are members of a short-chain dehydrogenase/reductase family of enzymes, we hypothesize that DHEA could be an antagonist of InhA. Our results demonstrate that DHEA has a direct microbicide effect against Mycobacterium tuberculosis; this effect was supported by in silico docking analysis and the molecular dynamic simulation studies between DHEA and InhA. Thus, DHEA increases the production of pro-inflammatory cytokines in the lung, inactivates GC by 11β-HSD1, and inhibits mycobacterial InhA. The multiple functions of DHEA suggest that this hormone or its synthetic analogs could be an efficient co-adjuvant for tuberculosis treatment.Fil: Hernández Bustamante, Israel. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Santander Plantamura, Yanina Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Reyes Chaparro, Andrés. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Toxicología; MéxicoFil: Bini, Estela Isabel. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Torre Villalvazo, Iván. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Tovar, Armando R.. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Barrios Payan, Jorge. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Marquina Castillo, Brenda. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; MéxicoFil: Carranza, Maria Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFrontiers Media2023-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/225064Hernández Bustamante, Israel; Santander Plantamura, Yanina Alejandra; Mata Espinosa, Dulce; Reyes Chaparro, Andrés; Bini, Estela Isabel; et al.; Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity; Frontiers Media; Frontiers in Endocrinology; 13; 1055430; 1-2023; 1-161664-2392CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2022.1055430info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fendo.2022.1055430/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-26T08:38:40Zoai:ri.conicet.gov.ar:11336/225064instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-26 08:38:40.667CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
title Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
spellingShingle Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
Hernández Bustamante, Israel
11Β-HYDROXYSTEROID DEHYDROGENASE
DEHYDROEPIANDROSTERONE
GLUCOCORTICOID
INFLAMMATION
INHA
LUNG
TUBERCULOSIS
TYPE 2 DIABETES MELLITUS
title_short Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
title_full Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
title_fullStr Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
title_full_unstemmed Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
title_sort Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity
dc.creator.none.fl_str_mv Hernández Bustamante, Israel
Santander Plantamura, Yanina Alejandra
Mata Espinosa, Dulce
Reyes Chaparro, Andrés
Bini, Estela Isabel
Torre Villalvazo, Iván
Tovar, Armando R.
Barrios Payan, Jorge
Marquina Castillo, Brenda
Hernández Pando, Rogelio
Carranza, Maria Andrea
author Hernández Bustamante, Israel
author_facet Hernández Bustamante, Israel
Santander Plantamura, Yanina Alejandra
Mata Espinosa, Dulce
Reyes Chaparro, Andrés
Bini, Estela Isabel
Torre Villalvazo, Iván
Tovar, Armando R.
Barrios Payan, Jorge
Marquina Castillo, Brenda
Hernández Pando, Rogelio
Carranza, Maria Andrea
author_role author
author2 Santander Plantamura, Yanina Alejandra
Mata Espinosa, Dulce
Reyes Chaparro, Andrés
Bini, Estela Isabel
Torre Villalvazo, Iván
Tovar, Armando R.
Barrios Payan, Jorge
Marquina Castillo, Brenda
Hernández Pando, Rogelio
Carranza, Maria Andrea
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 11Β-HYDROXYSTEROID DEHYDROGENASE
DEHYDROEPIANDROSTERONE
GLUCOCORTICOID
INFLAMMATION
INHA
LUNG
TUBERCULOSIS
TYPE 2 DIABETES MELLITUS
topic 11Β-HYDROXYSTEROID DEHYDROGENASE
DEHYDROEPIANDROSTERONE
GLUCOCORTICOID
INFLAMMATION
INHA
LUNG
TUBERCULOSIS
TYPE 2 DIABETES MELLITUS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Metabolic syndrome is considered the precursor of type 2 diabetes mellitus. Tuberculosis is a leading infection that constitutes a global threat remaining a major cause of morbi-mortality in developing countries. People with type 2 diabetes mellitus are more likely to suffer from infection with Mycobacterium tuberculosis. For both type 2 diabetes mellitus and tuberculosis, there is pulmonary production of anti-inflammatory glucocorticoids mediated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal hormone dehydroepiandrosterone (DHEA) counteracts the glucocorticoid effects of cytokine production due to the inhibition of 11β-HSD1. Late advanced tuberculosis has been associated with the suppression of the Th1 response, evidenced by a high ratio of cortisol/DHEA. In a murine model of metabolic syndrome, we determined whether DHEA treatment modifies the pro-inflammatory cytokines due to the inhibition of the 11β-HSD1 expression. Since macrophages express 11β-HSD1, our second goal was incubating them with DHEA and Mycobacterium tuberculosis to show that the microbicide effect was increased by DHEA. Enoyl-acyl carrier protein reductase (InhA) is an essential enzyme of Mycobacterium tuberculosis involved in the mycolic acid synthesis. Because 11β-HSD1 and InhA are members of a short-chain dehydrogenase/reductase family of enzymes, we hypothesize that DHEA could be an antagonist of InhA. Our results demonstrate that DHEA has a direct microbicide effect against Mycobacterium tuberculosis; this effect was supported by in silico docking analysis and the molecular dynamic simulation studies between DHEA and InhA. Thus, DHEA increases the production of pro-inflammatory cytokines in the lung, inactivates GC by 11β-HSD1, and inhibits mycobacterial InhA. The multiple functions of DHEA suggest that this hormone or its synthetic analogs could be an efficient co-adjuvant for tuberculosis treatment.
Fil: Hernández Bustamante, Israel. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Santander Plantamura, Yanina Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Mata Espinosa, Dulce. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Reyes Chaparro, Andrés. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzados. Departamento de Toxicología; México
Fil: Bini, Estela Isabel. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Torre Villalvazo, Iván. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Tovar, Armando R.. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Barrios Payan, Jorge. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Marquina Castillo, Brenda. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México
Fil: Carranza, Maria Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Metabolic syndrome is considered the precursor of type 2 diabetes mellitus. Tuberculosis is a leading infection that constitutes a global threat remaining a major cause of morbi-mortality in developing countries. People with type 2 diabetes mellitus are more likely to suffer from infection with Mycobacterium tuberculosis. For both type 2 diabetes mellitus and tuberculosis, there is pulmonary production of anti-inflammatory glucocorticoids mediated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The adrenal hormone dehydroepiandrosterone (DHEA) counteracts the glucocorticoid effects of cytokine production due to the inhibition of 11β-HSD1. Late advanced tuberculosis has been associated with the suppression of the Th1 response, evidenced by a high ratio of cortisol/DHEA. In a murine model of metabolic syndrome, we determined whether DHEA treatment modifies the pro-inflammatory cytokines due to the inhibition of the 11β-HSD1 expression. Since macrophages express 11β-HSD1, our second goal was incubating them with DHEA and Mycobacterium tuberculosis to show that the microbicide effect was increased by DHEA. Enoyl-acyl carrier protein reductase (InhA) is an essential enzyme of Mycobacterium tuberculosis involved in the mycolic acid synthesis. Because 11β-HSD1 and InhA are members of a short-chain dehydrogenase/reductase family of enzymes, we hypothesize that DHEA could be an antagonist of InhA. Our results demonstrate that DHEA has a direct microbicide effect against Mycobacterium tuberculosis; this effect was supported by in silico docking analysis and the molecular dynamic simulation studies between DHEA and InhA. Thus, DHEA increases the production of pro-inflammatory cytokines in the lung, inactivates GC by 11β-HSD1, and inhibits mycobacterial InhA. The multiple functions of DHEA suggest that this hormone or its synthetic analogs could be an efficient co-adjuvant for tuberculosis treatment.
publishDate 2023
dc.date.none.fl_str_mv 2023-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/225064
Hernández Bustamante, Israel; Santander Plantamura, Yanina Alejandra; Mata Espinosa, Dulce; Reyes Chaparro, Andrés; Bini, Estela Isabel; et al.; Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity; Frontiers Media; Frontiers in Endocrinology; 13; 1055430; 1-2023; 1-16
1664-2392
CONICET Digital
CONICET
url http://hdl.handle.net/11336/225064
identifier_str_mv Hernández Bustamante, Israel; Santander Plantamura, Yanina Alejandra; Mata Espinosa, Dulce; Reyes Chaparro, Andrés; Bini, Estela Isabel; et al.; Structural homology between 11 beta-hydroxysteroid dehydrogenase and Mycobacterium tuberculosis Inh-A enzyme: Dehydroepiandrosterone as a potential co-adjuvant treatment in diabetes-tuberculosis comorbidity; Frontiers Media; Frontiers in Endocrinology; 13; 1055430; 1-2023; 1-16
1664-2392
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fendo.2022.1055430
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fendo.2022.1055430/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.011256

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