Matrix metalloproteinases are down-regulated in rat lenses exposed to oxidative stress.
Matrix metalloproteinases are important biological effectors of tissue remodelling. Increased MMP expression occurs during injury, inflammation, cellular transformation, and oxidative stress. Oxidative stress in the lens, a causal factor in cataractogenesis, has been shown to induce MMP secretion. The objective of this study was to assess the expression of MMPs and their regulators in an oxidative stress model of cataract, where epithelial cell death and cortical fibre cell swelling occurs in rat lenses after exposure to riboflavin, oxygen, and light. Two time points (4 and 7 hr of exposure) were chosen in order to compare transparent lenses with partially opaque lenses. MMP activity, protein, and mRNA levels were measured. The results show that MMP-2, MMP-9, MT1-MMP, and MT3-MMP are down-regulated by oxidative stress and that the down-regulation is most likely due to reduced gene transcription. In contrast, genes for catalase, glutathione peroxidase, and GAPDH are essentially unaffected, while beta-actin mRNA and protein levels are markedly increased at both time points. The down-regulation of MMPs occurs in lenses still seemingly transparent after 4 hr of exposure, indicating that reduced MMP activity is a relatively early response to the oxidative stress. Moreover, in our model system, MMP inhibition, not induction, is associated with cataractogenesis.
John
Molykutty
M
Section of Molecular Therapeutics, National Eye Institute, National Institutes of Health, Building 7, Room 202, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Jaworski
Cynthia
C
Chen
Zhengguang
Z
Subramanian
Saradha
S
Ma
Wanchao
W
Sun
Fang
F
Li
Dayu
D
Spector
Abraham
A
Carper
Deborah
D
D000199:Actins / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000201:enzymology* / Q000378:metabolism; D015536:Down-Regulation; D007908:Lens, Crystalline / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D046509:Tissue Culture Techniques; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D000199:Actins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9