During ischemia/reperfusion (I/R), cardiomyocytes are exposed to sudden lack of nutrients and successively to radical oxygen species (ROS). In the present study, we used the HL-5 cardiac atrial myocyte cell line exposed to serum/glucose depletion added or not in H2O2 to mimic ROS during ischemia, then replaced in their standard culture medium to simulate reperfusion. We investigated the effects of serum/glucose depletion combined or not to ROS exposure on AKT and MAP kinases activation to address the role of each event with respect to apoptosis. We demonstrate that serum/glucose depletion per se did not induce apoptosis when compared to ROS exposure. In particular, ROS recruited p38MAPK and JNK pathways. SB202190 preventing p38MAPK activity, partially protected HL-5 from apoptosis while blocking JNK, thanks to JNKI, further enhanced apoptosis. Blocking phosphatidylinositol (PI) 3-kinase with LY294002 or ERKs with U0126 was without consequence on apoptosis. Finally, BCL-2 and BCL-XL/S expression levels were analyzed in cells exposed to 1 h ischemia followed by 12-h reperfusion in the presence or not of SB202190; BCL-2, but not BCL-XL/S, expression was decreased in ROS treated cells but SB202190 failed to restore BCL-2 level. Our data suggest that p38MAPK activation primarily mediates ROS-induced apoptosis while concomitant JNK activation would represent a scavenger pathway for cells trying to escape apoptosis. © 2003 Wiley-Liss, Inc.

Cicconi, S., Ventura, N., Pastore, D., Bonini, P., DI NARDO, P., Lauro, R., et al. (2003). Characterization of apoptosis signal transduction pathways in HL-5 cardiomyocytes exposed to ischemia/reperfusion oxidative stress model. JOURNAL OF CELLULAR PHYSIOLOGY [10.1002/jcp.10219].

Characterization of apoptosis signal transduction pathways in HL-5 cardiomyocytes exposed to ischemia/reperfusion oxidative stress model

VENTURA, NATASCIA;PASTORE, DONATELLA;DI NARDO, PAOLO;LAURO, RENATO;
2003-01-01

Abstract

During ischemia/reperfusion (I/R), cardiomyocytes are exposed to sudden lack of nutrients and successively to radical oxygen species (ROS). In the present study, we used the HL-5 cardiac atrial myocyte cell line exposed to serum/glucose depletion added or not in H2O2 to mimic ROS during ischemia, then replaced in their standard culture medium to simulate reperfusion. We investigated the effects of serum/glucose depletion combined or not to ROS exposure on AKT and MAP kinases activation to address the role of each event with respect to apoptosis. We demonstrate that serum/glucose depletion per se did not induce apoptosis when compared to ROS exposure. In particular, ROS recruited p38MAPK and JNK pathways. SB202190 preventing p38MAPK activity, partially protected HL-5 from apoptosis while blocking JNK, thanks to JNKI, further enhanced apoptosis. Blocking phosphatidylinositol (PI) 3-kinase with LY294002 or ERKs with U0126 was without consequence on apoptosis. Finally, BCL-2 and BCL-XL/S expression levels were analyzed in cells exposed to 1 h ischemia followed by 12-h reperfusion in the presence or not of SB202190; BCL-2, but not BCL-XL/S, expression was decreased in ROS treated cells but SB202190 failed to restore BCL-2 level. Our data suggest that p38MAPK activation primarily mediates ROS-induced apoptosis while concomitant JNK activation would represent a scavenger pathway for cells trying to escape apoptosis. © 2003 Wiley-Liss, Inc.
2003
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - MEDICINA INTERNA
English
Con Impact Factor ISI
ACTIVATED PROTEIN-KINASES; RAT VENTRICULAR MYOCYTES; ISCHEMIA-REPERFUSION INJURY; CULTURED CARDIAC MYOCYTES; CELL-DEATH; MYOCARDIAL-ISCHEMIA; REGULATED KINASES; PROMOTES SURVIVAL; DNA FRAGMENTATION; PERFUSED HEART
Cicconi, S., Ventura, N., Pastore, D., Bonini, P., DI NARDO, P., Lauro, R., et al. (2003). Characterization of apoptosis signal transduction pathways in HL-5 cardiomyocytes exposed to ischemia/reperfusion oxidative stress model. JOURNAL OF CELLULAR PHYSIOLOGY [10.1002/jcp.10219].
Cicconi, S; Ventura, N; Pastore, D; Bonini, P; DI NARDO, P; Lauro, R; Marlier, Lnjl
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/53037
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