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MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant injury in RPE: implications for extracellular matrix turnover.

Publication ,  Journal Article
Alcazar, O; Cousins, SW; Marin-Castaño, ME
Published in: Invest Ophthalmol Vis Sci
December 2007

PURPOSE: To investigate whether overexpression of MMP-14 and/or TIMP-2 would overcome the effect of nonlethal oxidant injury with hydroquinone (HQ) on MMP-2 activity. METHODS: Human MMP-14 and TIMP2 cDNA were cloned into a mammalian expression vector. Transient transfections were performed on human ARPE-19 cells. The cells were incubated 48 hours after transfection with a nonlethal dose of HQ for either 6 or 18 hours and then were collected for protein determination or RNA isolation. MMP-2 protein and activity were determined by Western blot and zymography. The extracellular matrix (ECM) components type I and type IV collagen and laminin were analyzed by Western blot analysis and real-time PCR. RESULTS: HQ for 6 hours modestly decreased MMP-2. MMP-2 recovered only after co-overexpression of MMP-14 and TIMP-2, but activity further decreased after HQ for 18 hours. MMP-14 or TIMP-2 overexpression alone contributed as much as the co-overexpression to the recovery of MMP-2 activity. MMP-2 protein seemed not to be altered. Type I collagen and laminin transcriptional levels remained unaffected, whereas type IV collagen transcripts decreased with HQ. Transfection with MMP-14 and/or TIMP-2 contributed to the return of type IV collagen levels to normal. On the other hand, type I and IV collagens and laminin protein accumulated after HQ treatment, an effect prevented by transfection. CONCLUSIONS: MMP-14 and TIMP2 contribute to the maintenance of adequate levels of MMP-2 activity in ARPE-19 cells after oxidant injury. In addition, changes in ECM components may result as a consequence of MMP-2 activity and may be relevant to the progression of dry AMD.

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Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

December 2007

Volume

48

Issue

12

Start / End Page

5662 / 5670

Location

United States

Related Subject Headings

  • Transfection
  • Tissue Inhibitor of Metalloproteinase-2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Pigment Epithelium of Eye
  • Ophthalmology & Optometry
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14
  • Laminin
  • Hydroquinones
  • Humans
 

Citation

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Alcazar, O., Cousins, S. W., & Marin-Castaño, M. E. (2007). MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant injury in RPE: implications for extracellular matrix turnover. Invest Ophthalmol Vis Sci, 48(12), 5662–5670. https://doi.org/10.1167/iovs.07-0392
Alcazar, Oscar, Scott W. Cousins, and Maria E. Marin-Castaño. “MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant injury in RPE: implications for extracellular matrix turnover.Invest Ophthalmol Vis Sci 48, no. 12 (December 2007): 5662–70. https://doi.org/10.1167/iovs.07-0392.
Alcazar O, Cousins SW, Marin-Castaño ME. MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant injury in RPE: implications for extracellular matrix turnover. Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5662–70.
Alcazar, Oscar, et al. “MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant injury in RPE: implications for extracellular matrix turnover.Invest Ophthalmol Vis Sci, vol. 48, no. 12, Dec. 2007, pp. 5662–70. Pubmed, doi:10.1167/iovs.07-0392.
Alcazar O, Cousins SW, Marin-Castaño ME. MMP-14 and TIMP-2 overexpression protects against hydroquinone-induced oxidant injury in RPE: implications for extracellular matrix turnover. Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5662–5670.

Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

December 2007

Volume

48

Issue

12

Start / End Page

5662 / 5670

Location

United States

Related Subject Headings

  • Transfection
  • Tissue Inhibitor of Metalloproteinase-2
  • Reverse Transcriptase Polymerase Chain Reaction
  • Pigment Epithelium of Eye
  • Ophthalmology & Optometry
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14
  • Laminin
  • Hydroquinones
  • Humans