Characterization of apoptosis signal transduction pathways in HL-5 cardiomyocytes exposed to ischemia/reperfusion oxidative stress model
✍ Scribed by Simona Cicconi; Natascia Ventura; Donatella Pastore; Paolo Bonini; Paolo Di Nardo; Renato Lauro; Lionel N.J.L. Marlier
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 403 KB
- Volume
- 195
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 H~2~O~2~ 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‐X~L/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‐X~L/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.