May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
ERK Activation Following Steroid Treatment of Lens Epithelial Cells
Author Affiliations & Notes
  • E.R. James
    Ophthalmology, Med Univ of South Carolina, Charleston, SC
  • L.L. Robertson
    Ophthalmology, Med Univ of South Carolina, Charleston, SC
  • Footnotes
    Commercial Relationships  E.R. James, None; L.L. Robertson, None.
  • Footnotes
    Support  NIH grants EY13786, EY14793, Research to Prevent Blindness Inc, MUSC–IRF–2004–05
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 1898. doi:
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      E.R. James, L.L. Robertson; ERK Activation Following Steroid Treatment of Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1898.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: The induction of posterior subcapsular cataracts (PSC) following steroid treatment is specific for glucocorticoids suggesting a role for glucocorticoid receptor (GR) activation. Lens epithelial cells contain a transcriptionally active GR that has been shown to be responsive to dexamethasone treatment and to affect the transcription of specific genes by both direct and indirect mechanisms. The range of potential effects generated through GR activation is broad and includes modulation of cell metabolism, differentiation, proliferation, migration and cell survival and the perturbation of several of these processes has been suggested to play a role in the development of PSC. Considerable evidence exists for the role of growth factors in lens epithelial cell proliferation and differentiation and development of the lens. One of the major mechanisms of action of growth factors is through the MAPK signal transduction pathways. In other cell types glucocorticoid administration has been shown to affect the MAPK activation. The purpose of this study was to determine if glucocorticoid treatment affects the state of MAPK activation in lens epithelial cells. Methods: Cultured human and rabbit lens epithelial cells, were exposed to dexamethasone (or DMSO solvent) and assayed for proliferation. Induction of specific genes noted from DNA array was confirmed by real–time PCR and protein expression by immunoblotting. The lens epithelial cells were assayed for ERK activation following FGF2 administration by immunoblotting and the transcription of the MAP kinase phosphatases 1 (MKP–1) and MKP–3 by real–time PCR. Results: Dexamethasone treatment induced a moderate increase in the rate of cell proliferation over 2 and 6 days of culture, and expression of specific proteins, including proliferating cell nuclear antigen, were enhanced. Several components of the MAPK and PI–3K pathways were upregulated and levels of SGK were sustainably elevated. Dexamethasone–treated cells exhibited enhanced levels of ERK1/2 activation relative to controls following stimulation with FGF2. Expression of MKP–1 was upregulated. Conclusions: The observed enhanced activation of FGF2–responsive ERK following dexamethasone treatment could play a role in modifying the proliferative potential of lens epithelial cells. The enhanced ERK activation occurred in spite of the moderately elevated expression of MKP–1, although MKP–3 levels may have been compensatory. The pro–survival protein, SGK, which was elevated following dexamethasone treatment, may have resulted either from the direct genomic action of activated GR or indirectly through ERK activation.

Keywords: receptors: pharmacology/physiology • cataract • corticosteroids 
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