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Abstract #9679 Published in IGR 5-3
Proteasome inhibition by chronic oxidative stress in human trabecular meshwork cells
Caballero M; Liton PB; Epstein DL; Gonzalez PBiochemical and Biophysical Research Communications 2003; 308: 346-352
The pathophysiological mechanisms leading to the malfunction of the trabecular meshwork (TM)-Schlemm's canal (SC) outflow pathway in glaucoma are still unclear. The authors hypothesize that chronic oxidative stress may contribute to the malfunction of the outflow pathway by impairing the intracellular proteasome system of the cells, decreasing the ability of the tissue to modulate outflow resistance. To study the effects of chronic oxidative stress on proteasome function, primary cultures of human TM cells were incubated under 40% oxygen and proteasome activity was analyzed by measuring the accumulation of enhanced green fluorescent protein fused to a PEST motif. Changes in proteasome content, cellular senescence, and cell viability were also monitored. After ten days of exposure to chronic oxidative stress, TM cells showed a marked decline in proteasome activity that was associated with premature senescence and decreased cell viability. These results suggest that proteasome failure may be involved in glaucoma pathophysiology.
Dr. M. Caballero, Department of Ophthalmology, Duke University, Durham, NC 27710, USA
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
