HEME OXYGENASE - EXPRESSION IN HUMAN RETINA AND MODULATION BY STRESS AGENTS IN A HUMAN RETINOBLASTOMA CELL MODEL SYSTEM

PCR and Southern blot analyses demonstrate that mRNA for heme oxygenase (HO), a well known "stress protein" in a number of tissues, is present in human retina. Western and northern blots show that the protein and mRNA are also expressed in human Y-79 retinoblastoma cells in culture and that the HO enzyme is rapidly induced by its substrate, heme. Moreover, HO is also induced by two chemicals, sodium arsenite and menadione, that act as agents of oxidative stress. HO is the regulatory enzyme in the heme degradative pathway and an increase in its activity could lead to the accumulation of bilirubin, an antioxidant, in the cell at the expense of heme, a prooxidant. The HO pathway may thus be of importance in protecting the retina against oxidative stress in vivo. Moreover, the Y-79 culture system should provide an excellent model for use in examining stress mechanisms in retinal cells at a molecular level.