title: Trypomastigotes and amastigotes of Trypanosoma cruzi induce apoptosis and STAT3 activation in cardiomyocytes in vitro.
abstract: The haemoflagellate Trypanosoma cruzi is the causative agent of Chagas' disease that occurs in approximately 8 million people in Latin America. Patients infected with T. cruzi frequently suffer of cardiomegaly and may die of myocardial failure. Here we show that T. cruzi trypomastigotes (extracellular form) increased in vitro apoptosis of rat cardiomyocytes. Additionally, we demonstrated that amastigotes (intracellular form), for which a method for purification was established, were also able to induce cardiomyocyte apoptosis. Increase of apoptosis was associated with up-regulation of the apoptotic gene bax by trypomastigotes, while expression of the anti-apoptotic gene bcl-2 was down-regulated by amastigotes. The transcription factor STAT3 but not STAT1 was activated in cardiomyocytes by trypomastigotes. In addition, tlr7 gene expression was up-regulated in cardiomyocytes incubated with trypomastigotes, suggesting that this Toll-like receptor is involved in the intracellular recognition after host cell invasion by T. cruzi. Glycosylphosphatidylinositols purified from trypomastigotes did not induce cardiomyocyte apoptosis and STAT activation but down-regulated tlr7 gene expression. In conclusion, cardiomyopathy observed in Chagas' disease might be in part due to apoptosis of cardiomyocytes induced directly by the parasite.
authors: Laboratory of Parasitology, Institute for Virology, Philipps University, 35043 Marburg, Germany.
authors: Philipp
authors: P
authors: Stahl
authors: Volker
authors: V
authors: Ruppert
authors: Thomas
authors: T
authors: Meyer
authors: Jörg
authors: J
authors: Schmidt
authors: Marco A
authors: MA
authors: Campos
authors: Ricardo T
authors: RT
authors: Gazzinelli
authors: Bernhard
authors: B
authors: Maisch
authors: Ralph T
authors: RT
authors: Schwarz
authors: Françoise
authors: F
authors: Debierre-Grockiego
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002598:Chagas Cardiomyopathy / Q000503:physiopathology*; D017261:Glycosylphosphatidylinositols / Q000494:pharmacology; D006790:Host-Parasite Interactions; D032383:Myocytes, Cardiac / Q000469:parasitology*; D051381:Rats; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis; D014349:Trypanosoma cruzi / Q000502:physiology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D017261:Glycosylphosphatidylinositols; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C489639:TLR7 protein, rat; D051199:Toll-Like Receptor 7; D051028:bcl-2-Associated X Protein