Abstract
Hydrogen peroxide (H 2O 2) is implicated in human cataract development. At the molecular level H 2O 2 has been observed to cause damage to DNA, protein and lipid. It is now demonstrated, for the first time in a lens system, that H 2O 2 at concentrations found in cataract patients induces expression of both c-jun and c-fos. At optimal concentrations of H 2O 2 mRNA accumulation of c-jun and c-fos in the rat lenses is induced 20- and 18-fold above normal levels respectively, but with distinct kinetics. This induction occurs at the transcriptional level. H 2O 2 also induces transactivation by activating protein-1 (AP-1) in rabbit lens epithelial cells. The antioxidant N-acetyl-cysteine (NAC) has a dual effect on the induction of c-jun and c-fos. Preincubation of rat lenses with 5 mM NAC inhibits the induction by H 2O 2, while 30 mM and 50 mM NAC induce expression of these genes and mask the H 2O 2 effect. H7 (50 μM), genistein (2 μM) and okadaic acid (20 nM), all block the induction of c-jun and c-fos mRNA accumulation in the H 2O 2-treated rat lenses. These results suggest that H 2O 2 activates protein kinase and phosphatase dependent signal transduction pathways to induce c-jun and c-fos expression which may regulate lens crystallin genes and other genes containing AP-1 binding sites.
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