Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells

Deborah A Ferrington, Tina N. Tran, Kathleen L. Lew, Holly Van Remmen, Dale S Gregerson

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent role in several retinal degenerative diseases, such as age-related macular degeneration, and with light damage. Strategies for preservation of vision that would interrupt the apoptotic cascade require understanding the molecular events associated with apoptosis. This study investigated the susceptibility of RPE to caspase-dependent and -independent apoptotic pathways when challenged with different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from wildtype and heterozygous mice with reduced levels of either Mn superoxide dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis through both caspase-independent and -dependent pathways, respectively. With both oxidants, translocation of apoptosis inducing factor into the nucleus was observed. Cells containing reduced levels of CuZnSOD were the most susceptible to oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas death receptor induced caspase-dependent apoptosis. These results show stimulus-specific activation of either the caspase-dependent or -independent pathway. Since cultured RPE express the protein components required for different apoptotic pathways, they provide a good model system for studying molecular events associated with multiple signals that lead to cell death.

Original languageEnglish (US)
Pages (from-to)638-650
Number of pages13
JournalExperimental Eye Research
Volume83
Issue number3
DOIs
StatePublished - Sep 1 2006

Fingerprint

Retinal Pigments
Caspases
Epithelial Cells
Oxidants
Apoptosis
Cytotoxic T-Lymphocytes
Cell Death
Apoptosis Inducing Factor
CD95 Antigens
Retinal Diseases
Death Domain Receptors
Peroxides
Macular Degeneration
Lymphocyte Activation
Superoxides
Anti-Idiotypic Antibodies
Light
Cell Line
Proteins

Keywords

  • apoptosis
  • cytotoxic T lymphocytes
  • fas
  • oxidation
  • retinal pigment epithelial cells

Cite this

Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells. / Ferrington, Deborah A; Tran, Tina N.; Lew, Kathleen L.; Van Remmen, Holly; Gregerson, Dale S.

In: Experimental Eye Research, Vol. 83, No. 3, 01.09.2006, p. 638-650.

Research output: Contribution to journalArticle

@article{d98c14810ce040e7b9853bb1cf55b7db,
title = "Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells",
abstract = "Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent role in several retinal degenerative diseases, such as age-related macular degeneration, and with light damage. Strategies for preservation of vision that would interrupt the apoptotic cascade require understanding the molecular events associated with apoptosis. This study investigated the susceptibility of RPE to caspase-dependent and -independent apoptotic pathways when challenged with different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from wildtype and heterozygous mice with reduced levels of either Mn superoxide dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis through both caspase-independent and -dependent pathways, respectively. With both oxidants, translocation of apoptosis inducing factor into the nucleus was observed. Cells containing reduced levels of CuZnSOD were the most susceptible to oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas death receptor induced caspase-dependent apoptosis. These results show stimulus-specific activation of either the caspase-dependent or -independent pathway. Since cultured RPE express the protein components required for different apoptotic pathways, they provide a good model system for studying molecular events associated with multiple signals that lead to cell death.",
keywords = "apoptosis, cytotoxic T lymphocytes, fas, oxidation, retinal pigment epithelial cells",
author = "Ferrington, {Deborah A} and Tran, {Tina N.} and Lew, {Kathleen L.} and {Van Remmen}, Holly and Gregerson, {Dale S}",
year = "2006",
month = "9",
day = "1",
doi = "10.1016/j.exer.2006.03.003",
language = "English (US)",
volume = "83",
pages = "638--650",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Different death stimuli evoke apoptosis via multiple pathways in retinal pigment epithelial cells

AU - Ferrington, Deborah A

AU - Tran, Tina N.

AU - Lew, Kathleen L.

AU - Van Remmen, Holly

AU - Gregerson, Dale S

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent role in several retinal degenerative diseases, such as age-related macular degeneration, and with light damage. Strategies for preservation of vision that would interrupt the apoptotic cascade require understanding the molecular events associated with apoptosis. This study investigated the susceptibility of RPE to caspase-dependent and -independent apoptotic pathways when challenged with different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from wildtype and heterozygous mice with reduced levels of either Mn superoxide dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis through both caspase-independent and -dependent pathways, respectively. With both oxidants, translocation of apoptosis inducing factor into the nucleus was observed. Cells containing reduced levels of CuZnSOD were the most susceptible to oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas death receptor induced caspase-dependent apoptosis. These results show stimulus-specific activation of either the caspase-dependent or -independent pathway. Since cultured RPE express the protein components required for different apoptotic pathways, they provide a good model system for studying molecular events associated with multiple signals that lead to cell death.

AB - Loss of retinal pigment epithelial (RPE) cells via apoptosis plays a prominent role in several retinal degenerative diseases, such as age-related macular degeneration, and with light damage. Strategies for preservation of vision that would interrupt the apoptotic cascade require understanding the molecular events associated with apoptosis. This study investigated the susceptibility of RPE to caspase-dependent and -independent apoptotic pathways when challenged with different stimuli, including oxidants, anti-Fas antibody, and activated cytotoxic T lymphocytes (CTLs). These experiments used novel RPE cell lines developed from wildtype and heterozygous mice with reduced levels of either Mn superoxide dismutatse (SOD) or CuZnSOD. Peroxide and 4-hydroxynonenal induced apoptosis through both caspase-independent and -dependent pathways, respectively. With both oxidants, translocation of apoptosis inducing factor into the nucleus was observed. Cells containing reduced levels of CuZnSOD were the most susceptible to oxidant-induced cell death. Targeted killing by CTLs and activation of the Fas death receptor induced caspase-dependent apoptosis. These results show stimulus-specific activation of either the caspase-dependent or -independent pathway. Since cultured RPE express the protein components required for different apoptotic pathways, they provide a good model system for studying molecular events associated with multiple signals that lead to cell death.

KW - apoptosis

KW - cytotoxic T lymphocytes

KW - fas

KW - oxidation

KW - retinal pigment epithelial cells

UR - http://www.scopus.com/inward/record.url?scp=33746922680&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746922680&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2006.03.003

DO - 10.1016/j.exer.2006.03.003

M3 - Article

C2 - 16682026

AN - SCOPUS:33746922680

VL - 83

SP - 638

EP - 650

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

IS - 3

ER -