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Hypoxia augments TNF-alpha-mediated endothelin-1 release and cell proliferation in human optic nerve head astrocytes
- Source :
- Biochemical and biophysical research communications. 318(3)
- Publication Year :
- 2004
-
Abstract
- The effect of hypoxia (24 h) on TNF-alpha-mediated release of endothelin-1 (ET-1) from human optic nerve head astrocytes (hONAs) and TNF-alpha- and ET-1-induced hONA proliferation was determined. ET-1 synthesis and release was quantitated using ELISA while TNF-alpha (10 nM)- and ET-1 (100 nM)-mediated hONA proliferation was assessed by CellTiter 96 aqueous one-solution cell proliferation assay, respectively. hONAs appeared to be more rounded with fewer processes following 24 h hypoxia compared to thodr seen in normoxia. Hypoxia enhanced TNF-alpha-mediated ET-1 synthesis and release (by 5-fold) and also significantly increased TNF-alpha- and ET-1-mediated hONA proliferation. PD142893 (1 microM), an ET(A/B) receptor antagonist, blocked ET-1-mediated hONA proliferation both under normoxia and hypoxia, while doing so only under normoxia following TNF-alpha treatment. Also, U0126 (10 microM; an upstream ERK1/2 inhibitor) completely blocked agonist-induced hONA proliferation in normoxia and partially blocked the same in hypoxia. These results demonstrate for the first time that hONAs secrete ET-1 and that TNF-alpha and hypoxia can regulate its levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF-alpha and ET-1. These agonist-mediated effects following hypoxia could contribute to astroglial activation as seen in glaucomatous optic nerve heads.
- Subjects :
- Endothelin Receptor Antagonists
medicine.medical_specialty
medicine.drug_class
Optic Disk
Biophysics
Biology
Endothelin-Converting Enzymes
Biochemistry
Internal medicine
Cell Line, Tumor
Nitriles
medicine
Butadienes
Aspartic Acid Endopeptidases
Humans
Secretion
Protease Inhibitors
Cycloheximide
Enzyme Inhibitors
Molecular Biology
Optic Nerve Heads
Cells, Cultured
Aged
Aged, 80 and over
Endothelin-1
Cell growth
Tumor Necrosis Factor-alpha
Glycopeptides
Metalloendopeptidases
Cell Biology
Anatomy
Hypoxia (medical)
Receptor antagonist
medicine.disease
Endothelin 1
Cell Hypoxia
Astrogliosis
Endocrinology
Astrocytes
Optic nerve
Dactinomycin
medicine.symptom
Mitogen-Activated Protein Kinases
Oligopeptides
Cell Division
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 318
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....76d204d746f49f059b1d16669787f199