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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Human retinal transmitochondrial cybrids with J or H mtDNA haplogroups respond differently to ultraviolet radiation: Implications for retinal diseases
PLoS ONE, Volume 9, No. 6, Article e99003, Year 2014
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Description
Background: It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings: Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance: In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be important to consider. © 2014 Malik et al.
Authors & Co-Authors
Malik, Deepika
United States, Irvine
University of California, Irvine
Hsu, Tiffany
United States, Irvine
University of California, Irvine
Falatoonzadeh, Payam
United States, Irvine
University of California, Irvine
Cáceres-del-Carpio, Javier Héctor
United States, Irvine
University of California, Irvine
Moustafa, M. Tarek
United States, Irvine
University of California, Irvine
Egypt, Minya
Minia University
Chwa, Marilyn M.
United States, Irvine
University of California, Irvine
Atilano, Shari R.
United States, Irvine
University of California, Irvine
Ramírez, Claudio
United States, Irvine
University of California, Irvine
Nesburn, Anthony B.M.D.
United States, Irvine
University of California, Irvine
United States, Los Angeles
Cedars-sinai Medical Center
Boyer, David
United States, Beverly Hills
Retina-vitreous Associates Medical Group
Kuppermann, Baruch D.
United States, Irvine
University of California, Irvine
Jazwinski, S. Michal
United States, New Orleans
Tulane University School of Medicine
Miceli, Michael V.
United States, New Orleans
Tulane University School of Medicine
Wallace, Douglas C.
United States, Philadelphia
University of Pennsylvania
Udar, Nitin S.
United States, Irvine
University of California, Irvine
Kenney, M. Cristina
United States, Irvine
University of California, Irvine
Statistics
Citations: 32
Authors: 16
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0099003
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Design
Cross Sectional Study