Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein.

We have recently reported that Trypanosoma cruzi infection protects cardiomyocytes against apoptosis induced by growth factor deprivation. Cruzipain, a major parasite antigen, reproduced this survival effect by a Bcl-2-dependent mechanism. In this study, we have investigated the molecular mechanisms of cruzipain-induced cardiomyocyte protection. Neonatal BALB/c mouse cardiac myocytes were cultured under minimum serum conditions in the presence of cruzipain or T. cruzi (Tulahuen strain). Some cultures were pretreated with the phosphatidylinositol 3-kinase (PI3K) inhibitor Ly294002 or specific inhibitors of the mitogen-activated protein kinase (MAPK) family members such as the mitogen-activated protein kinase kinase (MEK1) inhibitor PD098059, Jun N-terminal kinase (JNK) inhibitor SP600125, p38 MAPK inhibitor SB203580. Inhibition of PI3K and MEK1 but not JNK or p38 MAPK increased the apoptotic rate of cardiomyocytes treated with cruzipain. Phosphorylation of Akt, a major target of PI3K, and ERK1/2, MEK1-targets, was achieved at 15 min and 5 min, respectively. In parallel, these kinases were strongly phosphorylated by T. cruzi infection. In cultures treated with cruzipain, cleavage of caspase 3 was considerably diminished after serum starvation; Bcl-2 overexpression was inhibited by PD098059 but not by Ly294002, whereas Bad phosphorylation and Bcl-xL expression were increased and differentially modulated by both inhibitors. The results suggest that cruzipain exerts its anti-apoptotic property in cardiac myocytes at least by PI3K/Akt and MEK1/ERK1/2 signaling pathways. We further identified a differential modulation of Bcl-2 family members by these two signaling pathways.

Caracterización de Nóveles Componentes en los caminos de Transducción de señales por MAP-quinasas (MAPKs)

Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations primed by changes in the expression of a set of immediate early genes that include members of the AP-1 family of transcription factors. The Activating Protein 1 (AP-1) is a family of proteins composed by the Fos and Jan. sub-families. Several members of the Jim and Fos protein families play a central role in the transduction of environmental stimuli to the nucleus, as they are substrates for the Mitogen Activated Protein Kiaases (MAPKs). Stress Activated Protein Kisases (SAPKjs), are a subgroup of MAPKs, which include JNK kinase) and several p38 isoforms named p38ot, p38-l p38f, and p38o. Although activated bv receptor-linked signaling pathways, they constitute the main target for different sources of stress like changes the osniolarify of the media, inhibition of protein synthesis or UV radiation. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been largely studied, whereas a role lor Fos proteins in UV-mediated responses and the identification of Fos activating kinases las remained conti’oversial. In this study, we have identified f>38 MAPKs as. proteins that can associate with Fos auct phosphorylate Its transactivatioti both in vitro said in vivo, This phosphorj-latioii is transduced, in changes in its transcriptional capability as p38-activated Fos induces AP1-dtiven gene expression. Moreover, our findings indicate that p38 MAPKs mediate c-Fos In response to UV light in parallel to the effect of JNK UV-induced c-jun phosphorylation and transcriptioiiai activation.

Caracterización de Nóveles Componentes en los caminos de Transducción de señales por MAP-quinasas (MAPKs)

Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations primed by changes in the expression of a set of immediate early genes that include members of the AP-1 family of transcription factors. The Activating Protein 1 (AP-1) is a family of proteins composed by the Fos and Jan. sub-families. Several members of the Jim and Fos protein families play a central role in the transduction of environmental stimuli to the nucleus, as they are substrates for the Mitogen Activated Protein Kiaases (MAPKs). Stress Activated Protein Kisases (SAPKjs), are a subgroup of MAPKs, which include JNK kinase) and several p38 isoforms named p38ot, p38|l p38f, and p38o. Although activated bv receptor-linked signaling pathways, they constitute the main target for different sources of stress like changes the osniolarify of the media, inhibition of protein synthesis or UV radiation. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been largely studied, whereas a role lor Fos proteins in UV-mediated responses and the identification of Fos activating kinases las remained contioversial. In this study, we have identified f>38 MAPKs as. proteins that can associate with Fos auct phosphorylate Its transactivatioti both in vitro said in vivo, This phosphorj-latioii is transduced, in changes in its transcriptional capability as p38-activated Fos induces AP1-dtiven gene expression. Moreover, our findings indicate that p38 MAPKs mediate c-Fos In response to UV light in parallel to the effect of JNK UV-induced c-jun phosphorylation and transcriptioiiai activation.

Caracterización de Nóveles Componentes en los caminos de Transducción de señales por MAP-quinasas (MAPKs)

Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations primed by changes in the expression of a set of immediate early genes that include members of the AP-1 family of transcription factors. The Activating Protein 1 (AP-1) is a family of proteins composed by the Fos and Jan. sub-families. Several members of the Jim and Fos protein families play a central role in the transduction of environmental stimuli to the nucleus, as they are substrates for the Mitogen Activated Protein Kiaases (MAPKs). Stress Activated Protein Kisases (SAPKjs), are a subgroup of MAPKs, which include JNK kinase) and several p38 isoforms named p38ot, p38-l p38f, and p38o. Although activated bv receptor-linked signaling pathways, they constitute the main target for different sources of stress like changes the osniolarify of the media, inhibition of protein synthesis or UV radiation. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been largely studied, whereas a role lor Fos proteins in UV-mediated responses and the identification of Fos activating kinases las remained conti’oversial. In this study, we have identified f>38 MAPKs as. proteins that can associate with Fos auct phosphorylate Its transactivatioti both in vitro said in vivo, This phosphorj-latioii is transduced, in changes in its transcriptional capability as p38-activated Fos induces AP1-dtiven gene expression. Moreover, our findings indicate that p38 MAPKs mediate c-Fos In response to UV light in parallel to the effect of JNK UV-induced c-jun phosphorylation and transcriptioiiai activation.