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U. C. Welge-Lussen, K. Birke, N. Kopsachilis, F. Kruse, A. L. Yu; Alpha Lipoic Acid Inhibits Tgf-ß and Oxidative Stress Induced Poag Like Changes in Human Astrocytes by Inhibition of P38MAPK Pathway. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6099.
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Oxidative stress and transforming growth factor-beta 2 (TGF-β2) may play an important role in the pathogenesis of primary open angle glaucoma (POAG). Both factors are able to induce reactive oxygen species (ROS). The goal of the present study was to determine whether the antioxidant alpha-lipoic acid (ALA) could reduce hydrogen peroxide (H2O2) and TGF-β2-induced cellular changes in human optic nerve head (ONH) astrocytes in vitro and whether signal transduction pathways are influenced.
Cultured ONH astrocytes Cultured ONH astrocytes were pre-treated with different concentrations of ALA before exposure to 100, 200, and 400 µM hydrogen peroxide (H2O2) for 1 hour or treatment with 1.0 ng/ml TGF-β2 for 12, 24, and 48 hours. Expressions of αB-crystallin and Hsp27, fibronectin and connective tissue growth factor (CTGF) were examined by immunohistochemistry and real-time PCR analysis. Lipid peroxidation was measured by decrease of cis-parinaric acid fluorescence. To investigate the role of signal transduction proteins, cells were pretreated with the specific inhibitors SB203580, PD98059, U0126 and SP600125. Furthermore, induction of p38MAP kinase and its phosphorylated form were determined by western blot analyses.
TGF-β2 and H202 increased lipid peroxidation in cultured astrocytes. TGF-β2 and H2O2 induced expression of αB-crystallin, Hsp27, fibronectin and CTGF. Pretreatment of cells with different concentration of ALA reduced the H2O2- and TGF-β2 increased lipid peroxidation and the stimulated expression of the investigated proteins. H2O2 and TGF-β2 upregulated the phosphorylated p38MAP kinase. Pretreatment with ALA inhibited the activation of p38MAPK pathway.
Oxidative stress and TGF-β2 induced POAG like changes in cultured human ONH via activation of p38MAPK pathway in astrocytes. The effect can be prevented by pretreatment with ALA. Signal transduction analysis revealed inhibition of p38 MAPK pathway by ALA. Therefore the use of ALA seems to be promising to prevent POAG like changes in human astocytes.
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