Anti-apoptotic protein survivin plays a significant role in tubular morphogenesis of human coronary arteriolar endothelial cells by hypoxic preconditioning.
Brief exposure of endothelial cells to oxidative stress induced by hypoxia followed by reoxygenation enhances tube formation. Our study provides evidence that hypoxic preconditioning accelerates tubular morphogenesis along with the activation of reactive oxygen species-inducible nuclear transcription factor-kappaB (NF-kappaB), phosphatidylinositol 3-kinase (PI3-kinase) and broad-spectrum anti-apoptotic protein survivin in human coronary arteriolar endothelial cells (HCAEC). The formation of tubular morphogenesis was inhibited by using the PI3-kinase and NF-kappaB antagonists LY294002 and SN50 respectively. The activation of survivin by hypoxic preconditioning was also inhibited by LY294002 and SN50 along with increased apoptosis in HCAEC. These data demonstrate a crucial role of PI3-kinase/Akt/NF-kappaB/survivin signaling in tubular morphogenesis of HCAEC triggered by hypoxic preconditioning.
Zhu
L
L
Molecular Cardiology Laboratory, Department of Surgery, Cardiovascular Research Center, University of Connecticut Medical School, Farmington, CT 06030-1110, USA.
Fukuda
S
S
Cordis
G
G
Das
D K
DK
Maulik
N
N
D017209:Apoptosis; D001160:Arterioles / Q000166:cytology; D015687:Cell Hypoxia; D002867:Chromones / Q000494:pharmacology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003331:Coronary Vessels / Q000166:cytology*; D004247:DNA / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008315:Malondialdehyde / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D009024:Morphogenesis; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009363:Neoplasm Proteins; D009389:Neovascularization, Pathologic; D018384:Oxidative Stress; D010455:Peptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction; D000077022:Survivin
D002867:Chromones; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008315:Malondialdehyde; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077022:Survivin; C107489:BIRC5 protein, human; C118258:SN50 peptide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one