scholarly journals Bioactivity Profiles of Cytoprotective Short-Chain Quinones

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1382
Author(s):  
Zikai Feng ◽  
Monila Nadikudi ◽  
Krystel L. Woolley ◽  
Ayman L. Hemasa ◽  
Sueanne Chear ◽  
...  
Keyword(s):  
Molecular Level ◽  
Short Chain ◽  
Redox Activity ◽  
Selection Strategy ◽  
Cytoprotective Activity ◽  
Reversible Redox ◽  
Human Hepatocarcinoma Cell Line ◽  
Mitochondrial Complex I Inhibitor ◽  
Bioactivity Profile ◽  
Hepatocarcinoma Cell Line

Short-chain quinones (SCQs) have been investigated as potential therapeutic candidates against mitochondrial dysfunction, which was largely thought to be associated with the reversible redox characteristics of their active quinone core. We recently reported a library of SCQs, some of which showed potent cytoprotective activity against the mitochondrial complex I inhibitor rotenone in the human hepatocarcinoma cell line HepG2. To better characterize the cytoprotection of SCQs at a molecular level, a bioactivity profile for 103 SCQs with different compound chemistries was generated that included metabolism related markers, redox activity, expression of cytoprotective proteins and oxidative damage. Of all the tested endpoints, a positive correlation with cytoprotection by SCQs in the presence of rotenone was only observed for the NAD(P)H:quinone oxidoreductase 1 (NQO1)-dependent reduction of SCQs, which also correlated with an acute rescue of ATP levels. The results of this study suggest an unexpected mode of action for SCQs that appears to involve a modification of NQO1-dependent signaling rather than a protective effect by the reduced quinone itself. This finding presents a new selection strategy to identify and develop the most promising compounds towards their clinical use.

scholarly journals Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones

2020 ◽  
Vol 13 (8) ◽  
pp. 184
Author(s):  
Zikai Feng ◽  
Mohammed Sedeeq ◽  
Abraham Daniel ◽  
Monika Corban ◽  
Krystel L. Woolley ◽  
...  
Keyword(s):  
Short Chain ◽  
Clinical Use ◽  
In Vitro Toxicology ◽  
Drug Candidates ◽  
Hepatocarcinoma Cell ◽  
Reversible Redox ◽  
Human Hepatocarcinoma Cell Line ◽  
Increased Sensitivity ◽  
Hepatocarcinoma Cell Line

Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, 1–11, from a library of SCQs that demonstrated enhanced cytoprotection and improved metabolic stability compared to the clinically used benzoquinone idebenone. Since the toxicity properties of our promising SCQs were unknown, this study developed multiplex methods and generated detailed toxicity profiles from 11 endpoint measurements using the human hepatocarcinoma cell line HepG2. Overall, the toxicity profiles were largely comparable across different assays, with simple standard assays showing increased sensitivity compared to commercial toxicity assays. Within the 11 naphthoquinones tested, the L-phenylalanine derivative 4 consistently demonstrated the lowest toxicity across all assays. The results of this study not only provide useful information about the toxicity features of SCQs but will also enable the progression of the most promising drug candidates towards their clinical use.

scholarly journals Electron Inventory of the Iron-Sulfur Scaffold Complex HypCD Essential in [NiFe]-Hydrogenase Cofactor Assembly

2021 ◽  
Author(s):  
Sven T. Stripp ◽  
Jonathan Oltmanns ◽  
Christina S. Müller ◽  
David Ehrenberg ◽  
Ramona Schlesinger ◽  
...  
Keyword(s):  
Redox Reactions ◽  
Redox Activity ◽  
Construction Site ◽  
Iron Ion ◽  
Paramagnetic Resonance ◽  
Iron Sulfur ◽  
Reducing Conditions ◽  
Reversible Redox ◽  
Electron Paramagnetic ◽  
Redox Conversion

The [4Fe-4S] cluster containing scaffold complex HypCD is the central construction site for the assembly of the [Fe](CN)2CO cofactor precursor of [NiFe]-hydrogenase. While the importance of the HypCD complex is well established, not much is known about the mechanism by which the CN– and CO ligands are transferred and attached to the iron ion. We developed an efficient protocol for the production and isolation of the functional HypCD complex that facilitated detailed spectroscopic investigations. The results obtained by UV/Vis-, electron paramagnetic Resonance (EPR)-, Resonance Raman-, Fourier-transform infrared (FTIR), and Mössbauer spectroscopy provide comprehensive evidence for an electron inventory fit to drive multi-electron redox reactions. We demonstrate the redox activity of the HypCD complex reporting the interconversion of the [4Fe-4S]2+/+ couple. Additionally, we observed a reversible redox conversion between the [4Fe-4S]2+ and a [3Fe-4S]+ cluster. MicroScale thermophoresis indicated preferable binding between the HypCD complex and its interaction partner HypEF under reducing conditions. Together, these results suggest a redox cascade involving the [4Fe-4S] cluster and a conserved disulfide bond of HypD that may facilitate the synthesis of the [Fe](CN)2CO cofactor precursor on the HypCD scaffold complex.

A TTFV–pyrene-based copolymer: synthesis, redox properties, and aggregation behaviour

RSC Advances ◽  
2015 ◽  
Vol 5 (30) ◽  
pp. 23952-23956 ◽  
Author(s):  
Eyad A. Younes ◽  
Kerry-Lynn M. Williams ◽  
Joshua C. Walsh ◽  
Celine M. Schneider ◽  
Graham J. Bodwell ◽  
...  
Keyword(s):  
Ph Value ◽  
Redox Properties ◽  
The Self ◽  
Redox Activity ◽  
Repeat Units ◽  
Aggregation Behaviour ◽  
Reversible Redox ◽  
Conjugated Copolymer ◽  
External Stimuli ◽  
Self Aggregation

A new π-conjugated copolymer containing tetrathiafulvalene vinylogue and pyrene repeat units was synthesized and exhibited reversible redox activity, while the self-aggregation behaviour in the solution phase was responsive to external stimuli such as solvent and pH value.

scholarly journals Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1890
Author(s):  
Francesca Balzano ◽  
Giuseppe Garroni ◽  
Sara Cruciani ◽  
Emanuela Bellu ◽  
Silvia Dei Giudici ◽  
...  
Keyword(s):  
Stem Cell ◽  
Behavioral Changes ◽  
Cell Cycle Regulators ◽  
Stem Cell Proliferation ◽  
Cell Lineages ◽  
Hepatocarcinoma Cell ◽  
Human Hepatocarcinoma Cell Line ◽  
Hepg2 Cell Lines ◽  
Hepatocarcinoma Cell Line ◽  
Senescence Associated Genes

Wharton jelly mesenchymal stem cells (WJ-MSCs) are able to differentiate into different cell lineages upon stimulation. This ability is closely related to the perfect balance between the pluripotency-related genes, which control stem-cell proliferation, and genes able to orchestrate the appearance of a specific phenotype. Here we studied the expression of stemness-related genes, epigenetic regulators (DNMT1, SIRT1), miRNAs (miR-145, miR-148, and miR-185) related to stemness, exosomes, the cell-cycle regulators p21 (WAF1/CIP1) and p53, and the senescence-associated genes (p16, p19, and hTERT). Cells were cultured in the presence or absence of the human hepatocarcinoma cell line HepG2-exhausted medium, to evaluate changes in stemness, differentiation capability, and senescence sensibility. Our results showed the overexpression of SIRT1 and reduced levels of p21 mRNA. Moreover, we observed a downregulation of DNMT1, and a simultaneous overexpression of Oct-4 and c-Myc. These findings suggest that WJ-MSCs are more likely to retain a stem phenotype and sometimes to switch to a highly undifferentiable proliferative-like behavior if treated with medium exhausted by human HepG2 cell lines.

Production of infectious ferret hepatitis E virus in a human hepatocarcinoma cell line PLC/PRF/5

2016 ◽  
Vol 213 ◽  
pp. 283-288 ◽  
Author(s):  
Tian-Cheng Li ◽  
Sayaka Yoshizaki ◽  
Tingting Yang ◽  
Michiyo Kataoka ◽  
Tomofumi Nakamura ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Hepatocarcinoma Cell ◽  
Human Hepatocarcinoma Cell Line ◽  
Hepatocarcinoma Cell Line

scholarly journals Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

2020 ◽  
Vol 6 (3) ◽  
pp. 75-86
Author(s):  
Veronika S. Belyaeva ◽  
Yulia V. Stepenko ◽  
Igor I. Lyubimov ◽  
Alexandr L. Kulikov ◽  
Alesia A. Tietze ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Vascular Wall ◽  
Foam Cells ◽  
Experimental Models ◽  
Short Chain ◽  
Inflammatory Factors ◽  
Cytoprotective Activity ◽  
Treatment And Prevention ◽  
And Migration

Relevance: Cardiovascular diseases continue to be the leading cause of premature adult death. Lipid profile and atherogenesis: Dislipidaemia leads to subsequent lipid accumulation and migration of immunocompetent cells into the vessel intima. Macrophages accumulate cholesterol forming foam cells – the morphological substrate of atherosclerosis in its initial stage. Inflammation and atherogenesis: Pro-inflammatory factors provoke oxidative stress, vascular wall damage and foam cells formation. Endothelial and mitochondrial dysfunction in the development of atherosclerosis: Endothelial mitochondria are some of the organelles most sensitive to oxidative stress. Damaged mitochondria produce excess superoxide and H2O2, which are the main factors of intracellular damage, further increasing endothelial dysfunction. Short non-hematopoietic erythropoietin-based peptides as innovative atheroprotectors: Research in recent decades has shown that erythropoietin has a high cytoprotective activity, which is mainly associated with exposure to the mitochondrial link and has been confirmed in various experimental models. There is also a short-chain derivative, the 11-amino acid pyroglutamate helix B surface peptide (PHBSP), which selectively binds to the erythropoietin heterodymic receptor and reproduces its cytoprotective properties. This indicates the promising use of short-chain derivatives of erythropoietin for the treatment and prevention of atherosclerotic vascular injury. In the future, it is planned to study the PHBSP derivatives, the modification of which consists in adding RGD and PGP tripeptides with antiaggregant properties to the original 11-member peptide.

Sign in / Sign up

Export Citation Format

Share Document