Document Detail


Retinal flavoprotein fluorescence correlates with mitochondrial stress, apoptosis, and chemokine expression.
MedLine Citation:
PMID:  21767533     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress and mitochondrial dysfunction occur before apoptosis in many retinal diseases. Under these conditions, a larger fraction of flavoproteins become oxidized and, when excited by blue-light, emit green flavoprotein fluorescence (FPF). In this study, we evaluated the utility of FPF as an early indicator of mitochondrial stress, pre-apoptotic cellular instability, and apoptosis of human retinal pigment epithelial (HRPE) cells subjected to hydrogen peroxide (H(2)O(2)) or monocytes (unstimulated or interferon-γ-stimulated) in vitro and of freshly-isolated pieces of human and rat neural retina subjected to H(2)O(2)ex vivo. Increased FPF of HRPE cells exposed to H(2)O(2) correlated with reduced mitochondrial membrane potential (ΔΨm) and increased apoptosis in a time- and dose-dependent manner. HRPE cells co-cultured with monocytes had increased FPF that correlated in a time-dependent manner with reduced ΔΨm, increased apoptosis, and early expression of pro-inflammatory chemokines, interleukin-8 (IL8) and monocyte chemotactic factor-1 (MCP1), which are known to be induced by oxidative stress. Increased FPF, reduced ΔΨm, and upregulation of IL8 and MCP1 occurred as early as 1-2 h after exposure to stressors, while apoptosis did not occur in HRPE cells until later time points. The antioxidant, N-acetyl-cysteine (NAC), inhibited increased FPF and apoptosis of HRPE cells subjected to H(2)O(2). Increased FPF of human and rat neural retina also correlated with increased apoptosis. This study suggests that FPF is a useful measure of mitochondrial function in retinal cells and tissues and can detect early mitochondrial dysfunction that may precede apoptosis.
Authors:
Matthew G Field; Dongli Yang; Zong-Mei Bian; Howard R Petty; Victor M Elner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-13
Journal Detail:
Title:  Experimental eye research     Volume:  93     ISSN:  1096-0007     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-01     Completed Date:  2012-01-16     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  548-55     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis*
Chemokine CCL2 / metabolism
Chemokines / metabolism*
Coculture Techniques
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Flavoproteins / metabolism*
Fluorescence
Humans
Hydrogen Peroxide / pharmacology
Interferon-gamma / pharmacology
Interleukin-8 / metabolism
Membrane Potential, Mitochondrial
Mitochondrial Diseases / metabolism*
Monocytes / drug effects
Oxidative Stress / drug effects
Rats
Rats, Sprague-Dawley
Retinal Pigment Epithelium / metabolism,  pathology*
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Grant Support
ID/Acronym/Agency:
EY007003/EY/NEI NIH HHS; EY019986/EY/NEI NIH HHS; EY09441/EY/NEI NIH HHS; R01 EY009441-13/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/CCL2 protein, human; 0/Chemokine CCL2; 0/Chemokines; 0/Flavoproteins; 0/Interleukin-8; 7722-84-1/Hydrogen Peroxide; 82115-62-6/Interferon-gamma
Comments/Corrections

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