Oxidant-induced apoptosis in human retinal pigment epithelial cells: Dependence on extracellular redox state

Shunai Jiang, Siobhan E. Moriarty-Craige, Michael Orr, Jiyang Cai, Paul Sternberg, Dean P. Jones

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

PURPOSE. To test whether variation in extracellular cysteine (Cys) redox potential (Eh) over the physiologic range occurring in human plasma affects oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE) cells. METHODS. The hRPE cells were incubated in culture medium with Eh established over the range of -16 mV (most oxidized) to -158 mV (most reduced) by adding different concentrations of Cys and cystine (CySS) with constant total Cys equivalents. Apoptosis was induced with tert- butylhydroperoxide (tBH). RESULTS. The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized extracellular conditions (Eh > -55 mV) compared with the reduced conditions (Eh < -89 mV). Loss of mitochondrial membrane potential (Δψm), release of cytochrome c, and activation of caspase 3 after tBH treatments all increased under the more oxidized conditions. However, the extracellular redox state did not affect expression of Fas or FasL in hRPE cells. CONCLUSIONS. The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).

Original languageEnglish (US)
Pages (from-to)1054-1061
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

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Retinal Pigments
Oxidants
Oxidation-Reduction
Epithelial Cells
Apoptosis
tert-Butylhydroperoxide
Cysteine
Cystine
Mitochondrial Membrane Potential
Macular Degeneration
Cytochromes c
Caspase 3
Culture Media
Retina
Population

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Oxidant-induced apoptosis in human retinal pigment epithelial cells : Dependence on extracellular redox state. / Jiang, Shunai; Moriarty-Craige, Siobhan E.; Orr, Michael; Cai, Jiyang; Sternberg, Paul; Jones, Dean P.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 3, 03.2005, p. 1054-1061.

Research output: Contribution to journalArticle

Jiang, Shunai ; Moriarty-Craige, Siobhan E. ; Orr, Michael ; Cai, Jiyang ; Sternberg, Paul ; Jones, Dean P. / Oxidant-induced apoptosis in human retinal pigment epithelial cells : Dependence on extracellular redox state. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 3. pp. 1054-1061.
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abstract = "PURPOSE. To test whether variation in extracellular cysteine (Cys) redox potential (Eh) over the physiologic range occurring in human plasma affects oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE) cells. METHODS. The hRPE cells were incubated in culture medium with Eh established over the range of -16 mV (most oxidized) to -158 mV (most reduced) by adding different concentrations of Cys and cystine (CySS) with constant total Cys equivalents. Apoptosis was induced with tert- butylhydroperoxide (tBH). RESULTS. The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized extracellular conditions (Eh > -55 mV) compared with the reduced conditions (Eh < -89 mV). Loss of mitochondrial membrane potential (Δψm), release of cytochrome c, and activation of caspase 3 after tBH treatments all increased under the more oxidized conditions. However, the extracellular redox state did not affect expression of Fas or FasL in hRPE cells. CONCLUSIONS. The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).",
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T1 - Oxidant-induced apoptosis in human retinal pigment epithelial cells

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AU - Jiang, Shunai

AU - Moriarty-Craige, Siobhan E.

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AU - Cai, Jiyang

AU - Sternberg, Paul

AU - Jones, Dean P.

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N2 - PURPOSE. To test whether variation in extracellular cysteine (Cys) redox potential (Eh) over the physiologic range occurring in human plasma affects oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE) cells. METHODS. The hRPE cells were incubated in culture medium with Eh established over the range of -16 mV (most oxidized) to -158 mV (most reduced) by adding different concentrations of Cys and cystine (CySS) with constant total Cys equivalents. Apoptosis was induced with tert- butylhydroperoxide (tBH). RESULTS. The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized extracellular conditions (Eh > -55 mV) compared with the reduced conditions (Eh < -89 mV). Loss of mitochondrial membrane potential (Δψm), release of cytochrome c, and activation of caspase 3 after tBH treatments all increased under the more oxidized conditions. However, the extracellular redox state did not affect expression of Fas or FasL in hRPE cells. CONCLUSIONS. The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).

AB - PURPOSE. To test whether variation in extracellular cysteine (Cys) redox potential (Eh) over the physiologic range occurring in human plasma affects oxidant-induced apoptosis in cultured human retinal pigment epithelial (hRPE) cells. METHODS. The hRPE cells were incubated in culture medium with Eh established over the range of -16 mV (most oxidized) to -158 mV (most reduced) by adding different concentrations of Cys and cystine (CySS) with constant total Cys equivalents. Apoptosis was induced with tert- butylhydroperoxide (tBH). RESULTS. The hRPE cells were sensitized to tBH-induced apoptosis in the more oxidized extracellular conditions (Eh > -55 mV) compared with the reduced conditions (Eh < -89 mV). Loss of mitochondrial membrane potential (Δψm), release of cytochrome c, and activation of caspase 3 after tBH treatments all increased under the more oxidized conditions. However, the extracellular redox state did not affect expression of Fas or FasL in hRPE cells. CONCLUSIONS. The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).

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