Language:

Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy

Frontiers in immunology, 2021-11, Vol.12, p.755862-755862 [Peer Reviewed Journal]

Copyright © 2021 Nunes, Andrieux, Brochet, Almeida, Kitano, Honda, Iwai, Andrade-Silva, Goudenège, Alcântara Silva, Vieira, Levy, Bydlowski, Gallardo, Torres, Bocchi, Mano, Santos, Bacal, Pomerantzeff, Laurindo, Teixeira, Nakaya, Kalil, Procaccio, Chevillard and Cunha-Neto. ;Attribution ;Copyright © 2021 Nunes, Andrieux, Brochet, Almeida, Kitano, Honda, Iwai, Andrade-Silva, Goudenège, Alcântara Silva, Vieira, Levy, Bydlowski, Gallardo, Torres, Bocchi, Mano, Santos, Bacal, Pomerantzeff, Laurindo, Teixeira, Nakaya, Kalil, Procaccio, Chevillard and Cunha-Neto 2021 Nunes, Andrieux, Brochet, Almeida, Kitano, Honda, Iwai, Andrade-Silva, Goudenège, Alcântara Silva, Vieira, Levy, Bydlowski, Gallardo, Torres, Bocchi, Mano, Santos, Bacal, Pomerantzeff, Laurindo, Teixeira, Nakaya, Kalil, Procaccio, Chevillard and Cunha-Neto ;ISSN: 1664-3224 ;EISSN: 1664-3224 ;DOI: 10.3389/fimmu.2021.755862 ;PMID: 34867992

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy
Author: Nunes, João Paulo Silva ; Andrieux, Pauline ; Brochet, Pauline ; Almeida, Rafael Ribeiro ; Kitano, Eduardo ; Honda, André Kenji ; Iwai, Leo Kei ; Andrade-Silva, Débora ; Goudenège, David ; Alcântara Silva, Karla Deysiree ; Vieira, Raquel de Souza ; Levy, Débora ; Bydlowski, Sergio Paulo ; Gallardo, Frédéric ; Torres, Magali ; Bocchi, Edimar Alcides ; Mano, Miguel ; Santos, Ronaldo Honorato Barros ; Bacal, Fernando ; Pomerantzeff, Pablo ; Laurindo, Francisco Rafael Martins ; Teixeira, Priscila Camillo ; Nakaya, Helder I ; Kalil, Jorge ; Procaccio, Vincent ; Chevillard, Christophe ; Cunha-Neto, Edecio
Subjects: Adolescent ; Adult ; Aged ; Cellular Biology ; Chagas Cardiomyopathy - metabolism ; Chagas Cardiomyopathy - pathology ; Chagas Cardiomyopathy - physiopathology ; Child ; chronic Chagas disease cardiomyopathy ; energy metabolism ; Female ; Human health and pathology ; Humans ; Immunology ; Infectious diseases ; interferon gamma ; Interferon-gamma - metabolism ; Life Sciences ; Male ; Middle Aged ; mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; mitochondrial dysfunction ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - pathology ; Oxidative Stress - physiology ; Tumor Necrosis Factor-alpha - metabolism ; Young Adult
Is Part Of: Frontiers in immunology, 2021-11, Vol.12, p.755862-755862
Description: Infection by the protozoan causes Chagas disease cardiomyopathy (CCC) and can lead to arrhythmia, heart failure and death. Chagas disease affects 8 million people worldwide, and chronic production of the cytokines IFN-γ and TNF-α by T cells together with mitochondrial dysfunction are important players for the poor prognosis of the disease. Mitochondria occupy 40% of the cardiomyocytes volume and produce 95% of cellular ATP that sustain the life-long cycles of heart contraction. As IFN-γ and TNF-α have been described to affect mitochondrial function, we hypothesized that IFN-γ and TNF-α are involved in the myocardial mitochondrial dysfunction observed in CCC patients. In this study, we quantified markers of mitochondrial dysfunction and nitro-oxidative stress in CCC heart tissue and in IFN-γ/TNF-α-stimulated AC-16 human cardiomyocytes. We found that CCC myocardium displayed increased levels of nitro-oxidative stress and reduced mitochondrial DNA as compared with myocardial tissue from patients with dilated cardiomyopathy (DCM). IFN-γ/TNF-α treatment of AC-16 cardiomyocytes induced increased nitro-oxidative stress and decreased the mitochondrial membrane potential (ΔΨm). We found that the STAT1/NF-κB/NOS2 axis is involved in the IFN-γ/TNF-α-induced decrease of ΔΨm in AC-16 cardiomyocytes. Furthermore, treatment with mitochondria-sparing agonists of AMPK, NRF2 and SIRT1 rescues ΔΨm in IFN-γ/TNF-α-stimulated cells. Proteomic and gene expression analyses revealed that IFN-γ/TNF-α-treated cells corroborate mitochondrial dysfunction, transmembrane potential of mitochondria, altered fatty acid metabolism and cardiac necrosis/cell death. Functional assays conducted on Seahorse respirometer showed that cytokine-stimulated cells display decreased glycolytic and mitochondrial ATP production, dependency of fatty acid oxidation as well as increased proton leak and non-mitochondrial oxygen consumption. Together, our results suggest that IFN-γ and TNF-α cause direct damage to cardiomyocytes' mitochondria by promoting oxidative and nitrosative stress and impairing energy production pathways. We hypothesize that treatment with agonists of AMPK, NRF2 and SIRT1 might be an approach to ameliorate the progression of Chagas disease cardiomyopathy.
Publisher: Switzerland: Frontiers
Language: English
Identifier: ISSN: 1664-3224
EISSN: 1664-3224
DOI: 10.3389/fimmu.2021.755862
PMID: 34867992
Source: Hyper Article en Ligne (HAL) (Open Access)
GFMER Free Medical Journals
MEDLINE
PubMed Central
ROAD: Directory of Open Access Scholarly Resources
DOAJ Directory of Open Access Journals

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Co-Exposure of Cardiomyocytes to IFN-γ and TNF-α Induces Mitochondrial Dysfunction and Nitro-Oxidative Stress: Implications for the Pathogenesis of Chronic Chagas Disease Cardiomyopathy

Searching Remote Databases, Please Wait