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Journal of Cell Science 114, 4033-4040 (2001)
© 2001 The Company of Biologists Limited

RESEARCH ARTICLE

Potential role for laminin 5 in hypoxia-mediated apoptosis of human corneal epithelial cells

Miechia A. Esco1, Zhiyu Wang1, Mark L. McDermott2 and Michelle Kurpakus-Wheater1,*

1 Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, USA
2 Department of Ophthalmology, Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI, USA

*Author for correspondence (e-mail: mkurpaku{at}med.wayne.edu)

Accepted August 7, 2001

Laminin 5 functions to promote cell-matrix adhesion and therefore is hypothesized to abrogate apoptosis initiated through the loss of epithelial cell contact with extracellular matrix. Laminin 5 levels are decreased in epithelial cells cultured in a hypoxic environment. Exposure of epithelial cells to hypoxia may induce apoptotic pathways transmitted through changes in mitochondrial membrane potential. Using an apoptosis assay based on mitochondrial membrane integrity, the effect of hypoxia (2% oxygen) on human corneal epithelial cell viability was determined. Both a virally transformed corneal epithelial cell line and third passage corneal epithelial cells were resistant to hypoxia-mediated apoptosis for up to 5 days in culture. However, at 7 days in culture, a statistically significant increase in apoptosis was noted in hypoxic corneal epithelial cells compared to normoxic (20% oxygen) controls. Increased apoptosis in hypoxic epithelium at 7 days in culture correlated with decreased deposition of laminin 5 into the extracellular matrix, as determined by western blot analysis and immunofluorescence microscopy. Additionally, the extracellular processing of the {alpha}3 and {gamma}2 chains of laminin 5 was negatively impacted by corneal epithelial cell exposure to hypoxia for 7 days. Treatment of human corneal epithelial cells cultured in 20% oxygen with function-inhibiting antibodies to laminin 5 for 2 or 3 days resulted in a statistically significant decrease in proliferation, and concomitant increase in apoptosis, compared with untreated normoxic controls. Based on these results, it appears that mechanisms of hypoxia-mediated apoptosis in human corneal epithelial cells may be initiated by the loss of processed laminin 5 in the extracellular matrix or by the loss of laminin 5-epithelial cell communication and transmitted through mitochondria.

Key words: Apoptosis, Corneal epithelium, Hypoxia, Laminin 5




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[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2001