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Abstract #10615 Published in IGR 6-2
Hypoxia augments TNF-α-mediated endothelin-1 release and cell proliferation in human optic nerve head astrocytes
Desai D; He S; Yorio T; Krishnamoorthy R-R; Prasanna GBiochemical and Biophysical Research Communications 2004; 318: 642-8
The effect of hypoxia (24 h) on TNF-α-mediated release of endothelin-1 (ET-1) from human optic nerve head astrocytes (hONAs) and TNF-α- and ET-1-induced hONA proliferation was determined. ET-1 synthesis and release was quantitated using ELISA while TNF-α (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-α-mediated ET-1 synthesis and release (by 5-fold) and also significantly increased TNF-α- and ET-1-mediated hONA proliferation. PD142893 (1 μM), an ETA/B receptor antagonist, blocked ET-1-mediated hONA proliferation both under normoxia and hypoxia, while doing so only under normoxia following TNF-α treatment. Also, U0126 (10 μM; 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-α and hypoxia can regulate its levels. Moreover, hypoxia augments the proliferative responses of hONAs to TNF-α and ET-1. These agonist-mediated effects following hypoxia could contribute to astroglial activation as seen in glaucomatous optic nerve heads.
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Classification:
2.15 Optic nerve (Part of: 2 Anatomical structures in glaucoma)
3.6 Cellular biology (Part of: 3 Laboratory methods)
