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Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells.

Publication ,  Journal Article
Conley, SM; Bruhn, RL; Morgan, PV; Stamer, WD
Published in: Invest Ophthalmol Vis Sci
February 2004

PURPOSE: Because of the observed increase in incidence of glaucoma among some individuals taking selenium as a dietary supplement, the present study was undertaken to investigate mechanisms of selenium-induced changes in homeostasis of human trabecular meshwork (HTM) cells. Specifically, the impact of selenium on matrix metalloproteinases (MMPs), their inhibitors (tissue inhibitors of metalloproteinases; TIMPs), and the second messengers that regulate MMP expression was investigated in an HTM cell culture model. METHODS: HTM cell cultures were treated with an organic selenium compound (methyl seleninic acid), and changes in secretion and activity of MMPs and TIMPs were analyzed by Western blot and zymography. Changes in extracellular-signal-related kinases 1 and 2 (ERK1/2) and phospho-ERK1/2 levels were monitored by Western blot analysis of whole-cell lysates prepared from selenium-treated cells. Photographs of cultures over time were used to document selenium-induced changes in cell morphology. RESULTS: Treatment of HTM cells with selenium for 24 hours at doses ranging from 1 to 10 micro M caused a dose-dependent decrease in the secretion of MMP-2 and TIMP-1. Treatment for 6 hours revealed a significant decrease in MMP-2 and TIMP-1 at the highest dose. MMP-1, -3, and -9 and TIMP-2 were either not detected or their secretion was not consistently influenced by selenium treatment. Selenium treatment caused a significant decrease in ERK1/2 phosphorylation, but no change in overall ERK protein levels. Selenium treatment resulted in dose-dependent, reversible changes in HTM cell-matrix associations. CONCLUSIONS: Selenium-induced changes in MMP-2/TIMP-1 secretion may alter the balance of extracellular matrix turnover in the conventional outflow pathway and cause an increase in intraocular pressure that eventually leads to glaucoma.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

February 2004

Volume

45

Issue

2

Start / End Page

473 / 479

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Tissue Inhibitor of Metalloproteinase-1
  • Phosphorylation
  • Organoselenium Compounds
  • Ophthalmology & Optometry
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Matrix Metalloproteinase 2
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Conley, S. M., Bruhn, R. L., Morgan, P. V., & Stamer, W. D. (2004). Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells. Invest Ophthalmol Vis Sci, 45(2), 473–479. https://doi.org/10.1167/iovs.03-0767
Conley, Shannon M., Roberta L. Bruhn, Parham V. Morgan, and W Daniel Stamer. “Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells.Invest Ophthalmol Vis Sci 45, no. 2 (February 2004): 473–79. https://doi.org/10.1167/iovs.03-0767.
Conley SM, Bruhn RL, Morgan PV, Stamer WD. Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):473–9.
Conley, Shannon M., et al. “Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells.Invest Ophthalmol Vis Sci, vol. 45, no. 2, Feb. 2004, pp. 473–79. Pubmed, doi:10.1167/iovs.03-0767.
Conley SM, Bruhn RL, Morgan PV, Stamer WD. Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):473–479.

Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

February 2004

Volume

45

Issue

2

Start / End Page

473 / 479

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Tissue Inhibitor of Metalloproteinase-1
  • Phosphorylation
  • Organoselenium Compounds
  • Ophthalmology & Optometry
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Matrix Metalloproteinase 2
  • Humans