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Role of Inhibitor of Apoptosis Protein 2 in Endothelial Postconditioning
Author(s) -
Noll Thomas,
Gadiraju Krishnaveni,
Gündüz Dursun,
Härtel Frauke Viola
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.820.16
Background Postconditioning (PC), intermittent hypoxia (H) at the onset of reperfusion (R), a strategy known to effectively reduce reperfusion injury, is well proven in cardiomyocytes. Here the protective effect of PC in endothelial cells was studied, focusing on the inhibitors of apoptosis proteins (IAPs). Methods and Results Exposure of cultured human umbilical vein endothelial cells to severe H (Po 2 <1 mmHg) for 2 h caused a 2.1±0.3‐fold increase in caspase‐3 cleavage and a 2.3±0.2‐fold increase in apoptosis 24h after R. However, PC (3 cycles of alternated H and R 5 min each), abolished H/R‐induced apoptosis. Protein content of cIAP2, but not its close homologue cIAP1 or XIAP, increased during H and was reduced to basal level with the onset of R. H as well as PC induced an interaction between cIAP2 and pocaspase‐3. Silencing of cIAP2 by specific siRNA enhanced H/R‐induced apoptosis and abolished the protective effect of PC. Maintenance of cIAP2 by PC in the intact vessel confirms the pathophysiological significance of the finding. Conclusions PC protects endothelial cells against H/R‐induced apoptosis. This protective effect is conferred by cIAP2, which is increasingly expressed during H and could be maintained at an elevated level by PC. Under these conditions cIAP2 binds to procaspase‐3 thereby inhibiting apoptosis of endothelial cells.