Oxidant-induced cell death in retinal pigment epithelium cells mediated through the release of apoptosis-inducing factor.

Journal Article (Journal Article)

In the present study, the pathways involved in oxidant-induced cell death of a primary cell of the retina, ARPE-19, were investigated and compared with a leukemic cell, U937 cells. Both ARPE-19 and U937 cells exhibited similar viability when exposed to menadione. At lethal doses, both cell lines demonstrated extensive membrane blebbing. However, although U937 cells exhibited caspase-3, -9 PARP cleavage and 200 bp laddering, no such cleavage or laddering was noted in ARPE-19 cells. Furthermore, addition of exogenous cytochrome c and ATP to a cell-free system again resulted in cleavage of caspase-3 and -9 in extracts of U937 but not ARPE cells. Further studies in ARPE-19 cells undergoing menadione-induced cell death demonstrated mitochondrial membrane depolarization, release of cytochrome c, nuclear translocation of apoptosis-inducing factor and subsequent 50 kilo-base pair laddering, and nuclear shrinkage. All of these findings were abrogated by the pretreatment of ARPE-19 cells with hepatocyte growth factor/scatter factor. These findings demonstrate the complex nature of cell death in primary cells of the retina and highlight the role of caspase-independent signals, growth factors and intracellular survival factors in programmed cell death pathways.

Full Text

Duke Authors

Cited Authors

  • Zhang, C; Baffi, J; Cousins, SW; Csaky, KG

Published Date

  • May 15, 2003

Published In

Volume / Issue

  • 116 / Pt 10

Start / End Page

  • 1915 - 1923

PubMed ID

  • 12668724

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.00390


  • eng

Conference Location

  • England