Yu, Alice L. and Fuchshofer, Rudolf and Birke, Marco and Priglinger, Siegfried G. and Eibl, Kirsten H. and Kampik, Anselm and Bloemendal, Hans and Welge-Lussen, Ulrich (2007) Hypoxia/reoxygenation and TGF-beta increase alpha B-crystallin expression in human optic nerve head astrocytes. EXPERIMENTAL EYE RESEARCH, 84 (4). pp. 694-706. ISSN 0014-4835, 1096-0007
Full text not available from this repository. (Request a copy)Abstract
Reactive astrocytes in glaucomatous optic nerve changes are characterized by an increased expression of alpha B-crystallin and transforming growth factor-beta (TGF-beta). In the pathogenesis of glaucomatous optic nerve damage, ischemia/reperfusion injury may play an important role. The goal of the present study was to determine the influence of hypoxia/reoxygenation and TGF-beta on the expression of alpha B-crystallin in cultured human astrocytes of the optic nerve head (ONH). Cultured human astrocytes were incubated under hypoxic conditions (1% O-2 for 4-12 h) with subsequent reoxygenation (12-24 h). Additionally, cells were treated with 1.0 ng/ml TGF-beta 1 and TGF-beta 2 for 12-48 h. Expression of alpha B-crystallin was examined by Northern- and Western-blotting. Levels of TGF-beta 1 and TGF-beta 2 were analyzed by RT-PCR analysis and ELISA. The effect of TGF-beta blocking on the hypoxia/reoxygenation modulated expression of alpha B-crystallin was investigated by simultaneous incubation with neutralizing antibodies against TGF-beta during the reoxygenation phase. Hypoxia/reoxygenation increased the expression of alpha B-crystallin at the mRNA (2.8- to 3.1-fold) and protein level (1.8- to 2.1-fold). Treatment with 1.0 ng/ml TGF-beta 1 and TGF-beta 2 for 12-48 h markedly enhanced alpha B-crystallin mRNA expression approximately three to fourfold. Using Western blot analysis, this increase ranged from 2 to 3 times. Both cytokines showed a twofold increase after 12 and 24 h of reoxygenation at the mRNA and a two- to threefold increase at the protein level. Simultaneous treatment with neutralizing antibodies against both TGF-beta isoforms prevented the hypoxia/reoxygenation-mediated elevation of alpha B-crystallin. The process of hypoxia/reoxygenation is capable of inducing the expression of alpha B-crystallin and TGF-beta in cultured ONH astrocytes. Therefore, optimization of conditions leading to hypoxia/reoxygenation in the ONH of glaucomatous patients may help to lower the incidence of characteristic changes in the optic nerve. (c) 2006 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; HUMAN LAMINA-CRIBROSA; SHOCK PROTEINS; TRABECULAR MESHWORK; STRESS-PROTEINS; TRANSFORMING GROWTH-FACTOR-BETA-2; OCULAR HYPERTENSION; ALZHEIMERS-DISEASE; ANGLE GLAUCOMA; AQUEOUS-HUMOR; heat shock protein; optic nerve; astrocyte; transforming growth factor-beta; hypoxia; reoxygenation |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Dec 2020 07:49 |
| Last Modified: | 16 Dec 2020 07:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32939 |
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