Functional characterization of ATP7B mutant hepatic cell lines after copper exposure

2016 ◽  
Vol 06 (03) ◽  
Author(s):  
Hartmut Schmidt
Keyword(s):  
Cell Lines ◽  
Functional Characterization ◽  
Hepatic Cell ◽  
Copper Exposure ◽  
Hepatic Cell Lines

scholarly journals Cyclin-dependent kinase 19 upregulation correlates with an unfavorable prognosis in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaopeng Cai ◽  
Jingwen Deng ◽  
Jiaming zhou ◽  
Huiqiang Cai ◽  
Zhi Chen
Keyword(s):  
Cell Lines ◽  
Transcriptional Activation ◽  
Prognostic Value ◽  
Immune Cell ◽  
Functional Characterization ◽  
Hepatic Cell ◽  
Migration And Invasion ◽  
Cyclin Dependent Kinase ◽  
Hub Genes ◽  
Hepatic Cell Lines

Abstract Objectives Cyclin-dependent kinase 19 (CDK19) is a component of the mediator coactivator complex, which is required for transcriptional activation. In this study, we utilized public databases and wet-bench hepatic cell line experiments to elucidate the potential roles of CDK19 in hepatocellular cancer (HCC). Materials and methods We studied the relationships between CDK19 expression and several clinical features related to HCC via the Oncomine and UALCAN databases. The prognostic value of CDK19 was tested using the Kaplan–Meier Plotter database. We presented the mutations of CDK19 and addressed the relation of CDK19 expression with immune cell infiltration by means of the cBioPortal, Catalogue of Somatic Mutations in Cancer (COSMIC) and Tumor IMmune Estimation Resource (TIMER) databases. Hub genes were obtained and further analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. To test the in silico findings, we knocked down CDK19 with short hairpin RNA (shRNA) technology in two hepatic cell lines and conducted several functional characterization experiments. Results Marked CDK19 upregulation was found in HCC tissues versus normal liver tissues, and CDK19 mRNA expression had high diagnostic value in HCC patients. Subgroup analysis showed that CDK19 overexpression was associated with sex, tumor stage and TP53 mutation status. The prognostic value of CDK19 upregulation for overall survival (OS) was significant in patients with stage 2–3, stage 3–4, and grade 2 disease. One percent of the patients had CDK19 mutations, but no relationship between CDK19 mutation and prognosis was observed. CDK19 was positively correlated with the abundances of CD4 + T cells, macrophages and dendritic cells. We identified 10 genes correlated with CDK19, 8 of which presented excellent prognostic value in HCC. These hub genes were directly involved in cell division and regulation of the G2/M cell cycle transition. Protein–protein interaction (PPI) and pathway predictions indicated that CDK19 is highly likely to be involved in several cellular functions, such as proliferation, migration, and invasion. These functions were strongly interfered from two independent hepatic cell lines after CDK19 knockdown. Conclusions CDK19 could be a prognostic marker in HCC, and its therapeutic potential in HCC needs further study.

Characterization of trans-immortalized hepatic cell lines established from transgenic mice

1991 ◽  
Vol 195 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Frédéric Perraud ◽  
Wilfried Dalemans ◽  
Jean-Louis Gendrault ◽  
Dominique Dreyer ◽  
Dalila Ali-Hadji ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cell Lines ◽  
Hepatic Cell ◽  
Hepatic Cell Lines

scholarly journals Cyclin Dependent Kinase 19 Upregulation Correlates With Unfavorable Prognosis in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Xiaopeng Cai ◽  
Jingwen Deng ◽  
Jiaming zhou ◽  
Huiqiang Cai ◽  
Zhi Chen
Keyword(s):  
Cell Lines ◽  
Transcriptional Activation ◽  
Prognostic Value ◽  
Functional Characterization ◽  
Hepatic Cell ◽  
Migration And Invasion ◽  
Cyclin Dependent Kinase ◽  
Hub Genes ◽  
Public Data ◽  
Hepatic Cell Lines

Abstract Objectives: Cyclin dependent kinase 19 (CDK19) is a component of the Mediator co-activator complex, which is required for transcriptional activation. In this study, we will utilize the public data and combine it with wet-bench experiments in hepatic cell lines to elucidate the potential roles of CDK19 in hepatocellular cancer (HCC).Materials and Methods: We studied the relationships between CDK19 expression and several clinical features related with HCC by consulting Oncomine and UALCAN. The prognostic value of CDK19 was tested using the Kaplan‐Meier Plotter database. We presented the mutations of CDK19 and addressed its relations with immune cells with the use of cBioPortal, and COSMIC and TIMER database. Hub genes were obtained and further analysed using the STRING database. To test the in silico findings, we knocked down CDK19 with short hairpin RNA (shRNA) technology in two hepatic cell lines, and then several functional characterization experiments were conducted. Results: A remarkably higher level of CDK19 expression was found in HCC tissues than normal liver tissues, and CDK19 mRNA expression has high diagnostic value in HCC patients. Subgroup analysis showed that CDK19 overexpression were associated with gender, tumor stage and TP53 mutant. Prognostic values of CDK19 upregulation for overall survival (OS) were significant in patients with stage 2-3, stage 3-4, grade 2 and etc. 1% of the patients have mutations at CDK19, and we did not observe a potential relationship between CDK19 mutation and prognosis. CDK19 showed positive correlations with the abundances of CD4+ T cells, macrophages and dendritic cells. We identified 10 genes that correlated with CDK19, 8 of which presented excellent prognostic value in HCC. Besides, these hub genes were directly involved in cell division and regulation of G2/M transition of mitotic cell cycle. PPI and pathway predictions indicated that CDK19 should have a high possibility to be involved with several cellular functions, such as proliferation, migration, and invasion. These functions were strongly interfered in two independent hepatic cell lines, after knocking down CDK19. Conclusions: CDK19 could serve as a prognostic marker in HCC and it deserves further work to test its therapeutic potential to HCC.

Establishment and characterization of a novel method for evaluating gluconeogenesis using hepatic cell lines, H4IIE and HepG2

2009 ◽  
Vol 491 (1-2) ◽  
pp. 46-52 ◽  
Author(s):  
Takashi Okamoto ◽  
Naohide Kanemoto ◽  
Takashi Ban ◽  
Toshiki Sudo ◽  
Keisuke Nagano ◽  
...  
Keyword(s):  
Cell Lines ◽  
Hepatic Cell ◽  
Novel Method ◽  
Hepatic Cell Lines

Cytotoxicity of anisidine in hepatic cell lines

2015 ◽  
Vol 53 (01) ◽  
Author(s):  
S Caliskan ◽  
F Wewering ◽  
B Gerding ◽  
A Luch ◽  
S Zellmer
Keyword(s):  
Cell Lines ◽  
Hepatic Cell ◽  
Hepatic Cell Lines

scholarly journals NFB-01. FUNCTIONAL CHARACTERIZATION OF ATRX LOSS IN NF1-ASSOCIATED GLIOMA AND MPNST

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii417-iii418
Author(s):  
Ming Yuan ◽  
Karlyne Reilly ◽  
Christine Pratilas ◽  
Christopher Heaphy ◽  
Fausto Rodriguez
Keyword(s):  
Cell Lines ◽  
Functional Characterization ◽  
Tert Promoter ◽  
Aggressive Tumors ◽  
Sirna Knockdown ◽  
Nih 3T3 ◽  
Vitro Effect ◽  
Murine Glioma

Abstract To identify the biologic relevance of ATRX loss in NF1-associated gliomagenesis, we studied the effects of Atrx loss using four previously characterized Nf1+/-Trp53+/- murine glioma lines. Lines 130G#3 and 158D#8 (corresponding to grade IV and III gliomas, respectively) displayed preserved ATRX protein expression compared to NIH-3T3 cells. We studied the effects of Atrx knockdown in these two lines in the presence and absence of the TERT inhibitor, BIRBR1532. Using a telomere-specific FISH assay, we identified increased signal intensity after Atrx knockdown, only in the presence of the TERT inhibitor. These features are reminiscent of ALT, although there were no significant alterations in cell growth. Next, we studied the effect of ATRX loss in MPNST lines ST88-14, NF90-8, STS-26T. These cell lines all expressed ATRX and DAXX. However, STS-26T contained a TERT promoter mutation and ST88-14 had a known SNP in the TERT promoter, while NF90-8 had no alterations. ATRX siRNA knockdown showed no significant effects in cell proliferation or apoptosis. However, ATRX knockdown resulted in rare ultra-bright foci, indicative of ALT. Next, we studied the in vitro effect of the ATR inhibitor VE-821 in MPNST cell lines. Only NF90-8 (lacking TERT alterations) demonstrated a decrease in growth after ATRX knockdown and VE-821 treatment. However, ATRX knockdown alone did not affect sensitivity to carboplatin. Our findings further support a role for ATRX loss with subsequent ALT activation in a biologic subset of NF1-associated malignancies, thereby opening an opportunity for therapeutic targeting of these aggressive tumors using specific classes of drugs.

scholarly journals Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1605
Author(s):  
Carlos Fernandes ◽  
Afonso J. C. Videira ◽  
Caroline D. Veloso ◽  
Sofia Benfeito ◽  
Pedro Soares ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Mitochondrial Membrane ◽  
Hepatic Cell ◽  
Therapeutic Application ◽  
Extracellular Acidification ◽  
Mitochondrial Oxidative Stress ◽  
Drug Candidates ◽  
Cellular Oxygen ◽  
Hepatic Cell Lines

Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ1 and with two non-targeted antioxidants, resveratrol and coenzyme Q10 (CoQ10). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ10, while MC4 and MC7.2 displayed around 100–1000× less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.

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