FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4221036981> ?p ?o ?g. }

• W4221036981 endingPage "109013" @default.
• W4221036981 startingPage "109013" @default.
• W4221036981 abstract "Mitochondrial dysfunction is associated with several retinal degenerative diseases including Age-related Macular Degeneration (AMD). Human mitochondrial DNA (mtDNA) haplogroups are inherited from a common ancestral clan and are defined by specific sets of genetic differences. The purpose of this study was to determine and compare the effects of mtDNA haplogroups H and J on transcriptome regulation and cellular resilience to oxidative stress in human RPE cytoplasmic hybrid (cybrid) cell lines in vitro. ARPE-19 cybrid cell lines containing mtDNA haplogroups H and J were created by fusing platelets obtained from normal individuals containing H and J haplogroups with mitochondria-deficient (Rho0) ARPE-19 cell lines. These cybrids were exposed to oxidative stress using 300 μM hydrogen peroxide (H2O2), following which mitochondrial structural dynamics was studied at varying time points using the mitochondrial markers - TOMM20 (Translocase of Outer Mitochondrial Membrane 20) and Mitotracker. To evaluate mitochondrial function, levels of ROS, ΔΨm and [Ca2+]m were measured using flow cytometry, and ATP levels were measured using luminescence. The H and J cybrid cell transcriptomes were compared using RNAseq to determine how changes in mtDNA regulate gene expression. Inflammatory and angiogenic markers were measured using Luminex assay to understand how these mtDNAs influenced cellular response to oxidative stress. Actin filaments’ morphology was examined using confocal microscopy. Following exposure to H2O2 stress, the J cybrids showed increased mitochondrial swelling and perinuclear localization, disturbed fission and fusion, increased calcium uptake (p < 0.05), and higher secreted levels of TNF-α and VEGF (p < 0.001), compared to the H cybrids. Calcium uptake by J cybrids was reduced using an IP3R inhibitor. Thirteen genes involved in mitochondrial complex I and V function, fusion/fission events, cellular energy homeostasis, antioxidant defenses, and inflammatory responses, were significantly downregulated with log2 fold changes ranging between −1.5 and −5.1. Actin levels were also significantly reduced in stressed J cybrids (p ≤ 0.001) and disruption in actin filaments was observed. Thirty-eight genes involved in mitochondrial and cellular support functions, were upregulated with log2 fold changes of +1.5 to +5.9 in J cybrids compared to H cybrids. Our results demonstrate significant structural and functional differences between mtDNA haplogroups H vs. J -containing cybrid cells. Our study suggests that the J mtDNA haplogroup can alter the transcriptome to increase cellular susceptibility to stress and retinal degenerations." @default.
• W4221036981 created "2022-04-03" @default.
• W4221036981 creator A5017321296 @default.
• W4221036981 creator A5045792511 @default.
• W4221036981 creator A5047466153 @default.
• W4221036981 creator A5050064000 @default.
• W4221036981 creator A5056785032 @default.
• W4221036981 creator A5058934024 @default.
• W4221036981 creator A5075683156 @default.
• W4221036981 date "2022-06-01" @default.
• W4221036981 modified "2023-10-04" @default.
• W4221036981 title "Differential mitochondrial and cellular responses between H vs. J mtDNA haplogroup-containing human RPE transmitochondrial cybrid cells" @default.
• W4221036981 cites W1512580658 @default.
• W4221036981 cites W1569332557 @default.
• W4221036981 cites W1590142351 @default.
• W4221036981 cites W1607763659 @default.
• W4221036981 cites W1889275428 @default.
• W4221036981 cites W1966828661 @default.
• W4221036981 cites W1970473512 @default.
• W4221036981 cites W1970650626 @default.
• W4221036981 cites W1972601476 @default.
• W4221036981 cites W1974396693 @default.
• W4221036981 cites W1977829186 @default.
• W4221036981 cites W1983873751 @default.
• W4221036981 cites W1985471315 @default.
• W4221036981 cites W1986720672 @default.
• W4221036981 cites W1988961100 @default.
• W4221036981 cites W1999053124 @default.
• W4221036981 cites W2002771508 @default.
• W4221036981 cites W2013647315 @default.
• W4221036981 cites W2018185503 @default.
• W4221036981 cites W2020407889 @default.
• W4221036981 cites W2020935669 @default.
• W4221036981 cites W2022367303 @default.
• W4221036981 cites W2033703236 @default.
• W4221036981 cites W2033836926 @default.
• W4221036981 cites W2034963123 @default.
• W4221036981 cites W2035330181 @default.
• W4221036981 cites W2036140173 @default.
• W4221036981 cites W2038511818 @default.
• W4221036981 cites W2051723837 @default.
• W4221036981 cites W2060822439 @default.
• W4221036981 cites W2062957434 @default.
• W4221036981 cites W2066300012 @default.
• W4221036981 cites W2068048197 @default.
• W4221036981 cites W2068568687 @default.
• W4221036981 cites W2071272327 @default.
• W4221036981 cites W2072082955 @default.
• W4221036981 cites W2072486096 @default.
• W4221036981 cites W2077992148 @default.
• W4221036981 cites W2085396235 @default.
• W4221036981 cites W2101300328 @default.
• W4221036981 cites W2105754268 @default.
• W4221036981 cites W2109291482 @default.
• W4221036981 cites W2111668248 @default.
• W4221036981 cites W2115406637 @default.
• W4221036981 cites W2119261959 @default.
• W4221036981 cites W2121966499 @default.
• W4221036981 cites W2125443686 @default.
• W4221036981 cites W2128544710 @default.
• W4221036981 cites W2130026447 @default.
• W4221036981 cites W2131387907 @default.
• W4221036981 cites W2133036751 @default.
• W4221036981 cites W2138356122 @default.
• W4221036981 cites W2139233019 @default.
• W4221036981 cites W2139861422 @default.
• W4221036981 cites W2144846851 @default.
• W4221036981 cites W2147551208 @default.
• W4221036981 cites W2152165298 @default.
• W4221036981 cites W2152409391 @default.
• W4221036981 cites W2155236757 @default.
• W4221036981 cites W2163757074 @default.
• W4221036981 cites W2325753945 @default.
• W4221036981 cites W2525948328 @default.
• W4221036981 cites W2549565264 @default.
• W4221036981 cites W2587150427 @default.
• W4221036981 cites W2588443411 @default.
• W4221036981 cites W2776568122 @default.
• W4221036981 cites W2790645197 @default.
• W4221036981 cites W29490248 @default.
• W4221036981 cites W3016688264 @default.
• W4221036981 cites W3155026330 @default.
• W4221036981 cites W3211981353 @default.
• W4221036981 doi "https://doi.org/10.1016/j.exer.2022.109013" @default.
• W4221036981 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35283109" @default.
• W4221036981 hasPublicationYear "2022" @default.
• W4221036981 type Work @default.
• W4221036981 citedByCount "2" @default.
• W4221036981 countsByYear W42210369812022 @default.
• W4221036981 crossrefType "journal-article" @default.
• W4221036981 hasAuthorship W4221036981A5017321296 @default.
• W4221036981 hasAuthorship W4221036981A5045792511 @default.
• W4221036981 hasAuthorship W4221036981A5047466153 @default.
• W4221036981 hasAuthorship W4221036981A5050064000 @default.
• W4221036981 hasAuthorship W4221036981A5056785032 @default.
• W4221036981 hasAuthorship W4221036981A5058934024 @default.
• W4221036981 hasAuthorship W4221036981A5075683156 @default.
• W4221036981 hasBestOaLocation W42210369812 @default.

• next