BACKGROUND: PR39 is a proline- and arginine-rich peptide implicated in wound healing and myocardial ischemia protection. To determine the potential mechanisms of PR39 in ischemia, we examined the role of PR39 in hypoxia-induced apoptosis in vascular endothelial cells. METHODS AND RESULTS: Hypoxia results in an increase of apoptosis in bovine aortic endothelial cells (BAECs), as determined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling (TUNEL) analysis and caspase-3 activity. Hypoxia induced 66.2+/-2.7% TUNEL-positive cells, whereas in the presence of synthesized PR39 peptide, TUNEL-positive cells were reduced to 29.6+/-1.9% (P<0.05). After 24 hours of hypoxia, the addition of PR39 reduced caspase-3 activity to 3.17+/-0.47 pMol/min from 10.52+/-0.55 pMol/min in hypoxic BAECs. Moreover, PR39 increased inhibitor of apoptosis protein-2 (IAP-2) gene and protein expression by 3-fold in a time- and dose-dependent manner. The induction of IAP-2 by PR39 conferred an increase in IAP-2 gene transcription and IAP-2 mRNA stability. Furthermore, inhibiting IAP-2 with second mitochondria-derived activator of caspase (Smac) and with small interfering RNA targeting IAP-2 abrogated the ability of PR39 to reduce caspase-3 activity. CONCLUSIONS: We provide the first direct evidence for PR39 as an antiapoptotic factor in endothelial cells during hypoxia. These data suggest that PR39 inhibits hypoxia-induced apoptosis and decreases caspase-3 activity in endothelial cells through an increase of IAP-2 expression.
BACKGROUND: PR39 is a proline- and arginine-rich peptide implicated in wound healing and myocardial ischemia protection. To determine the potential mechanisms of PR39 in ischemia, we examined the role of PR39 in hypoxia-induced apoptosis in vascular endothelial cells. METHODS AND RESULTS:Hypoxia results in an increase of apoptosis in bovine aortic endothelial cells (BAECs), as determined by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling (TUNEL) analysis and caspase-3 activity. Hypoxia induced 66.2+/-2.7% TUNEL-positive cells, whereas in the presence of synthesized PR39 peptide, TUNEL-positive cells were reduced to 29.6+/-1.9% (P<0.05). After 24 hours of hypoxia, the addition of PR39 reduced caspase-3 activity to 3.17+/-0.47 pMol/min from 10.52+/-0.55 pMol/min in hypoxic BAECs. Moreover, PR39 increased inhibitor of apoptosis protein-2 (IAP-2) gene and protein expression by 3-fold in a time- and dose-dependent manner. The induction of IAP-2 by PR39 conferred an increase in IAP-2 gene transcription and IAP-2 mRNA stability. Furthermore, inhibiting IAP-2 with second mitochondria-derived activator of caspase (Smac) and with small interfering RNA targeting IAP-2 abrogated the ability of PR39 to reduce caspase-3 activity. CONCLUSIONS: We provide the first direct evidence for PR39 as an antiapoptotic factor in endothelial cells during hypoxia. These data suggest that PR39 inhibits hypoxia-induced apoptosis and decreases caspase-3 activity in endothelial cells through an increase of IAP-2 expression.
Authors: Qinhui Song; Xiaojin An; Dongmei Li; Neel R Sodha; Munir Boodhwani; Ye Tian; Frank W Sellke; Jian Li Journal: Microvasc Res Date: 2009-08-27 Impact factor: 3.514
Authors: Edwin J A Veldhuizen; Viktoria A F Schneider; Herfita Agustiandari; Albert van Dijk; Johanna L M Tjeerdsma-van Bokhoven; Floris J Bikker; Henk P Haagsman Journal: PLoS One Date: 2014-04-22 Impact factor: 3.240
Authors: Jun She; Arnaud Goolaerts; Jun Shen; Jing Bi; Lin Tong; Lei Gao; Yuanlin Song; Chunxue Bai Journal: J Cell Mol Med Date: 2012-12 Impact factor: 5.310