Hypoxia stimulates release of the soluble form of fas ligand that inhibits endothelial cell apoptosis.

Abstract

Fas ligand (FasL), an apoptosis-inducing cytokine, is constitutively expressed on endothelial cells (EC). Here, we report that the soluble form of FasL (sFasL) is released from EC and inhibits hypoxia-induced EC apoptosis. For hypoxia experiments, human EC were exposed to low oxygen tension in airtight chambers flushed with preanalyzed gas mixtures (1% oxygen, 5% CO2, 94% N2) at 37 degrees C. Exposure of cultured EC to hypoxia transiently increased FasL mRNA and protein levels. The maximum increase was observed at 3 and 6 hours after exposure to hypoxia, respectively. Although sFasL protein was not detected in the supernatant from EC without hypoxia, sFasL protein level in the supernatant was transiently increased from 6 hours and disappeared again at 24 hours after the exposure to hypoxia. Interestingly, the supernatant from hypoxia-exposed EC inhibited EC apoptosis induced by hypoxia, which was abolished by a neutralizing antibody against FasL. In addition, incubation with KB8301, an inhibitor of metalloproteinase, suppressed the release of sFasL from EC and enhanced hypoxia-induced apoptosis in EC. Furthermore, exogenously added recombinant sFasL inhibited hypoxia-induced apoptosis. These findings indicate that sFasL released from EC may inhibit hypoxia-induced EC apoptosis. Therefore, the shedding of FasL could be a new therapeutic target in regulating hypoxia-induced EC injury.

• Authors: M Mogi, K Fukuo, J Yang, T Suhara, T Ogihara
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 81 Issue 2 Pg. 177-84 (Feb 2001) ISSN: 0023-6837 [Print] United States
• PMID: 11232639 (Publication Type: Journal Article)

Chemical References

• CASP8 and FADD-Like Apoptosis Regulating Protein
• CFLAR protein, human
• Carrier Proteins
• Cflar protein, mouse
• FASLG protein, human
• Fas Ligand Protein
• Fasl protein, mouse
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• fas Receptor

Topics

• Animals
• Apoptosis (physiology)
• CASP8 and FADD-Like Apoptosis Regulating Protein
• Carrier Proteins (genetics)
• Cell Hypoxia (physiology)
• Cells, Cultured
• Endothelium, Vascular (cytology, physiology)
• Fas Ligand Protein
• Gene Expression Regulation (physiology)
• Humans
• Intracellular Signaling Peptides and Proteins
• Membrane Glycoproteins (genetics, physiology)
• Mice
• Protein Biosynthesis
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription, Genetic
• Umbilical Veins
• fas Receptor (physiology)