Early Trypanosoma cruzi Infection Triggers mTORC1-Mediated Respiration Increase and Mitochondrial Biogenesis in Human Primary Cardiomyocytes

Frontiers in Microbiology
M Gabriela LibischCarlos Robello

Abstract

Chagasic chronic cardiomyopathy is one of the most frequent and severe manifestations of Chagas disease, caused by the parasite Trypanosoma cruzi. The pathogenic and biochemical mechanisms responsible for cardiac lesions remain not completely understood, although it is clear that hypertrophy and subsequent heart dilatation is in part caused by the direct infection of cardiomyocytes. In this work, we evaluated the initial response of human cardiomyocytes to T. cruzi infection by transcriptomic profiling. Immediately after infection, cardiomyocytes dramatically change their gene expression patterns, up regulating most of the genes encoding for respiratory chain, oxidative phosphorylation and protein synthesis. We found that these changes correlate with an increase in basal and maximal respiration, as well as in spare respiratory capacity, which is accompanied by mitochondrial biogenesis pgc-1α independent. We also demonstrate that these changes are mediated by mTORC1 and reversed by rapamycin, resembling the molecular mechanisms described for the non-chagasic hypertrophic cardiomyopathy. The results of the present work identify that early during infection, the activation of mTORC1, mitochondrial biogenesis and improvement in oxid...Continue Reading

References

Dec 1, 1990·Circulation·S A MorrisJ P Bilezikian
Sep 1, 1985·Molecular and Biochemical Parasitology·V T ContrerasS Goldenberg
Feb 1, 1986·American Heart Journal·A C Pereira BarrettoF Pileggi
Mar 1, 1995·São Paulo Medical Journal = Revista Paulista De Medicina·M D Higuchi
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·M V ChuenkovaM A Pereira
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 24, 2003·Journal of Cell Science·Aaron M WoolseyBarbara A Burleigh
Jul 29, 2003·Journal of Cardiovascular Pharmacology·Shoko MiuraKunio Shirato
Jun 16, 2004·Biochimica Et Biophysica Acta·Galina VyatkinaNisha Garg
May 5, 2009·Progress in Cardiovascular Diseases·Herbert B TanowitzLouis M Weiss
Aug 19, 2009·Free Radical Biology & Medicine·Shivali GuptaNisha Jain Garg
Sep 5, 2009·Microbes and Infection·Regina Coeli Dos Santos GoldenbergDavid C Spray
Oct 9, 2009·Journal of Cell Science·Mathieu Laplante, David M Sabatini
Apr 20, 2010·Lancet·Anis RassiJosé Antonio Marin-Neto
Jun 24, 2010·Nature·José Rodrigues Coura, Pedro Albajar Viñas
Dec 16, 2010·Nature Reviews. Molecular Cell Biology·Roberto ZoncuDavid M Sabatini
Feb 4, 2011·The American Journal of Clinical Nutrition·Pablo J Fernandez-Marcos, Johan Auwerx
Feb 24, 2011·Infection and Immunity·Patricio A ManqueGregory A Buck
Feb 2, 2012·Cardiology in Review·Fabiana S MachadoHerbert B Tanowitz
Feb 22, 2012·FEMS Microbiology Reviews·Maria Cecilia Fernandes, Norma W Andrews
Jun 13, 2012·Tropical Medicine & International Health : TM & IH·Paulo Marcos Matta GuedesJoão Santana Silva
Aug 14, 2012·Cold Spring Harbor Perspectives in Biology·Philippe P Roux, Ivan Topisirovic
Oct 31, 2012·Expert Review of Anti-infective Therapy·Rajesh JayachandranJean Pieters
Jan 22, 2013·Cell Host & Microbe·Kacey L CaradonnaBarbara A Burleigh
Dec 24, 2013·International Journal of Antimicrobial Agents·Paula Faral-TelloCarlos Robello
Mar 15, 2014·Parasite : Journal De La Société Française De Parasitologie·Kevin M Bonney
May 9, 2014·BioMed Research International·María Laura ChiribaoCarlos Robello
Jan 16, 2015·Cell Cycle·Masahiro MoritaIvan Topisirovic
Aug 2, 2015·The Lancet Infectious Diseases·Jose A Pérez-MolinaRogelio López-Vélez
Jan 16, 2016·PLoS Neglected Tropical Diseases·Aniekanabassi N UdokoPius N Nde
Jan 19, 2016·Translation·Neethi Nandagopal, Philippe P Roux
Oct 31, 2016·Trends in Parasitology·Michael D Lewis, John M Kelly

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Citations

Feb 4, 2021·Parasitology Research·Sajad RashidiRaúl Manzano-Román
Oct 23, 2020·Frontiers in Genetics·Tiago Bruno Rezende de CastroGloria Regina Franco
Feb 1, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Fabio Marcelo CerbánClaudia Cristina Motran
Apr 8, 2021·PLoS Pathogens·Pilar T V FlorentinoCarlos F M Menck
Jul 6, 2021·Frontiers in Cellular and Infection Microbiology·María Gabriela LibischCarlos Robello

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Methods Mentioned

BETA
Infection
chips
Feature Extraction
PCR
electrophoresis
flow cytometry
Confocal microscopy
biopsies

Software Mentioned

Agilent Feature Extraction
96
GraphPad Prism
GeneSpring GX
XGe

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