scholarly journals Analysis of Mitochondrial DNA Polymorphisms in the Human Cell Lines HepaRG and SJCRH30

2019 ◽  
Vol 20 (13) ◽  
pp. 3245 ◽  
Author(s):  
Matthew J. Young ◽  
Anitha D. Jayaprakash ◽  
Carolyn K. J. Young
Keyword(s):  
Mitochondrial Dna ◽  
Cell Lines ◽  
Human Cell ◽  
Cell Types ◽  
Dna Polymorphisms ◽  
Reference Sequence ◽  
Sequencing Analysis ◽  
Human Cell Lines ◽  
Mtdna Sequences ◽  
Mtdna Variants

The mitochondrial DNA (mtDNA) sequences of two commonly used human cell lines, HepaRG and SJCRH30, were determined. HepaRG originates from a liver tumor obtained from a patient with hepatocarcinoma and hepatitis C while SJCRH30 originates from a rhabdomyosarcoma patient tumor. In comparison to the revised Cambridge Reference Sequence, HepaRG and SJCRH30 mtDNA each contain 14 nucleotide variations. In addition to an insertion of a cytosine at position 315 (315insC), the mtDNA sequences from both cell types share six common polymorphisms. Heteroplasmic variants were identified in both cell types and included the identification of the 315insC mtDNA variant at 42 and 75% heteroplasmy in HepaRG and SJCRH30, respectively. Additionally, a novel heteroplasmic G13633A substitution in the HepaRG ND5 gene was detected at 33%. Previously reported cancer-associated mtDNA variants T195C and T16519C were identified in SJCRH30, both at homoplasmy (100%), while HepaRG mtDNA harbors a known prostate cancer-associated T6253C substitution at near homoplasmy, 95%. Based on our sequencing analysis, HepaRG mtDNA is predicted to lie within haplogroup branch H15a1 while SJCRH30 mtDNA is predicted to localize to H27c. The catalog of polymorphisms and heteroplasmy reported here should prove useful for future investigations of mtDNA maintenance in HepaRG and SJCRH30 cell lines.

Depletion of mitochondrial DNA by ddC in untransformed human cell lines

1997 ◽  
Vol 23 (4) ◽  
pp. 287-290 ◽  
Author(s):  
Isabelle Nelson ◽  
Michael G. Hanna ◽  
Nicholas W. Wood ◽  
A. E. Harding
Keyword(s):  
Mitochondrial Dna ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Lines

Cell cycle dependent morphology changes and associated mitochondrial DNA redistribution in mitochondria of human cell lines

Mitochondrion ◽  
2002 ◽  
Vol 1 (5) ◽  
pp. 425-435 ◽  
Author(s):  
Daciana H Margineantu ◽  
W Gregory Cox ◽  
Linda Sundell ◽  
Steven W Sherwood ◽  
Joseph M Beechem ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mitochondrial Dna ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Lines ◽  
Cycle Dependent ◽  
Morphology Changes

scholarly journals Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1966
Author(s):  
Italo Moglia ◽  
Margarita Santiago ◽  
Simon Guerrero ◽  
Mónica Soler ◽  
Alvaro Olivera-Nappa ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cell Lines ◽  
Cellular Uptake ◽  
Human Cell ◽  
Animal Experiments ◽  
Cell Types ◽  
Biological Properties ◽  
Human Cell Lines ◽  
Theranostic Agents

Gold nanoparticles (AuNP) capped with biocompatible layers have functional optical, chemical, and biological properties as theranostic agents in biomedicine. The ferritin protein containing in situ synthesized AuNPs has been successfully used as an effective and completely biocompatible nanocarrier for AuNPs in human cell lines and animal experiments in vivo. Ferritin can be uptaken by different cell types through receptor-mediated endocytosis. Despite these advantages, few efforts have been made to evaluate the toxicity and cellular internalization of AuNP-containing ferritin nanocages. In this work, we study the potential of human heavy-chain (H) and light-chain (L) ferritin homopolymers as nanoreactors to synthesize AuNPs and their cytotoxicity and cellular uptake in different cell lines. The results show very low toxicity of ferritin-encapsulated AuNPs on different human cell lines and demonstrate that efficient cellular ferritin uptake depends on the specific H or L protein chains forming the ferritin protein cage and the presence or absence of metallic cargo. Cargo-devoid apoferritin is poorly internalized in all cell lines, and the highest ferritin uptake was achieved with AuNP-loaded H-ferritin homopolymers in transferrin-receptor-rich cell lines, showing more than seven times more uptake than apoferritin.

scholarly journals Measurement and Detection of Mitochondrial DNA Deletions in Irradiated Human Cell Lines

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Shikha Gautam ◽  
Michelle Gulfo ◽  
Robert O'Donnell ◽  
Wendy Pogozelski
Keyword(s):  
Mitochondrial Dna ◽  
Cell Lines ◽  
Human Cell ◽  
Human Cell Lines ◽  
Dna Deletions

scholarly journals Exploring Chromosomal Structural Heterogeneity Across Multiple Cell Lines

2020 ◽  
Author(s):  
Ryan R. Cheng ◽  
Vinicius Contessoto ◽  
Erez Lieberman Aiden ◽  
Peter G. Wolynes ◽  
Michele Di Pierro ◽  
...  
Keyword(s):  
Cell Lines ◽  
Conformational Changes ◽  
Human Cell ◽  
Conformational Transition ◽  
Cell Types ◽  
Structural Heterogeneity ◽  
Human Cell Lines ◽  
Active Chromatin ◽  
State Process ◽  
Structural Ensembles

AbstractWe study the structural ensembles of human chromosomes across different cell types. Using computer simulations, we generate cell-specific 3D chromosomal structures and compare them to recently published chromatin structures obtained through microscopy. We demonstrate using a combination of machine learning and polymer physics simulations that epigenetic information can be used to predict the structural ensembles of multiple human cell lines. The chromosomal structures obtained in silico are quantitatively consistent with those obtained through microscopy as well as DNA-DNA proximity ligation assays. Theory predicts that chromosome structures are fluid and can only be described by an ensemble, which is consistent with the observation that chromosomes exhibit no unique fold. Nevertheless, our analysis of both structures from simulation and microscopy reveals that short segments of chromatin make transitions between a closed conformation and an open dumbbell conformation. This conformational transition appears to be consistent with a two-state process with an effective free energy cost of about four times the effective information theoretic temperature. Finally, we study the conformational changes associated with the switching of genomic compartments observed in human cell lines. Genetically identical but epigenetically distinct cell types appear to rearrange their respective structural ensembles to expose segments of transcriptionally active chromatin, belonging to the A genomic compartment, towards the surface of the chromosome, while inactive segments, belonging to the B compartment, move to the interior. The formation of genomic compartments resembles hydrophobic collapse in protein folding, with the aggregation of denser and predominantly inactive chromatin driving the positioning of active chromatin toward the surface of individual chromosomal territories.

scholarly journals SARS-CoV-2 disrupts proximal elements in the JAK-STAT pathway

2021 ◽  
Author(s):  
Da-Yuan Chen ◽  
Nazimuddin Khan ◽  
Brianna J. Close ◽  
Raghuveera K. Goel ◽  
Benjamin Blum ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Type I Interferon ◽  
Cell Types ◽  
Janus Kinase ◽  
Type I ◽  
Human Cell Lines ◽  
Interferon Signaling ◽  
Interferon Receptor ◽  
Stat Pathway

SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we generated a panel of phenotypically diverse, SARS-CoV-2-infectable human cell lines representing different body organs and performed longitudinal survey of cellular proteins and pathways broadly affected by the virus. This revealed universal inhibition of interferon signaling across cell types following SARS-CoV-2 infection. We performed systematic analyses of the JAK-STAT pathway in a broad range of cellular systems, including immortalized cells and primary-like cardiomyocytes, and found that SARS-CoV-2 targeted the proximal pathway components, including Janus kinase 1 (JAK1), tyrosine kinase 2 (Tyk2), and the interferon receptor subunit 1 (IFNAR1), resulting in cellular desensitization to type I IFN. Detailed mechanistic investigation of IFNAR1 showed that the protein underwent ubiquitination upon SARS-CoV-2 infection. Furthermore, chemical Inhibition of JAK kinases enhanced infection of stem cell-derived cultures, indicating that the virus benefits from inhibiting the JAK-STAT pathway. These findings suggest that the suppression of interferon signaling is a mechanism widely used by the virus to evade antiviral innate immunity, and that targeting the viral mediators of immune evasion may help block virus replication in patients with COVID-19. IMPORTANCE SARS-CoV-2 can infect various organs in the human body, but the molecular interface between the virus and these organs remains unexplored. In this study, we generated a panel of highly infectable human cell lines originating from various body organs and employed these cells to identify cellular processes commonly or distinctly disrupted by SARS-CoV-2 in different cell types. One among the universally impaired processes was interferon signaling. Systematic analysis of this pathway in diverse culture systems showed that SARS-CoV-2 targets the proximal JAK-STAT pathway components, destabilizes the type I interferon receptor though ubiquitination, and consequently renders the infected cells resistant to type I interferon. These findings illuminate how SARS-CoV-2 can continue to propagate in different tissues even in the presence of a disseminated innate immune response.

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