Carnoquinolines Target Copper Dyshomeostasis, Aberrant Protein–Protein Interactions, and Oxidative Stress

2020 ◽  
Vol 26 (70) ◽  
pp. 16690-16705
Author(s):  
Francesco Bellia ◽  
Giuseppa Ida Grasso ◽  
Ikhlas Mohamed Mohamud Ahmed ◽  
Valentina Oliveri ◽  
Graziella Vecchio
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Aberrant Protein ◽  
Copper Dyshomeostasis ◽  
And Oxidative Stress

scholarly journals SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress

Open Biology ◽  
2013 ◽  
Vol 3 (10) ◽  
pp. 120173 ◽  
Author(s):  
Ingrid Kassner ◽  
Anneli Andersson ◽  
Monika Fey ◽  
Martin Tomas ◽  
Elisa Ferrando-May ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Protein Function ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Protein Methyltransferase

ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo . ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo . Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.

scholarly journals Stability and sub-cellular localization of DNA polymerase β is regulated by interactions with NQO1 and XRCC1 in response to oxidative stress

2019 ◽  
Vol 47 (12) ◽  
pp. 6269-6286 ◽  
Author(s):  
Qingming Fang ◽  
Joel Andrews ◽  
Nidhi Sharma ◽  
Anna Wilk ◽  
Jennifer Clark ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Polymerase ◽  
Protein Interactions ◽  
Cellular Localization ◽  
Somatic Mutations ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Dna Polymerase Β ◽  
Enzyme Active Site ◽  
The Stability

Abstract Protein–protein interactions regulate many essential enzymatic processes in the cell. Somatic mutations outside of an enzyme active site can therefore impact cellular function by disruption of critical protein–protein interactions. In our investigation of the cellular impact of the T304I cancer mutation of DNA Polymerase β (Polβ), we find that mutation of this surface threonine residue impacts critical Polβ protein–protein interactions. We show that proteasome-mediated degradation of Polβ is regulated by both ubiquitin-dependent and ubiquitin-independent processes via unique protein–protein interactions. The ubiquitin-independent proteasome pathway regulates the stability of Polβ in the cytosol via interaction between Polβ and NAD(P)H quinone dehydrogenase 1 (NQO1) in an NADH-dependent manner. Conversely, the interaction of Polβ with the scaffold protein X-ray repair cross complementing 1 (XRCC1) plays a role in the localization of Polβ to the nuclear compartment and regulates the stability of Polβ via a ubiquitin-dependent pathway. Further, we find that oxidative stress promotes the dissociation of the Polβ/NQO1 complex, enhancing the interaction of Polβ with XRCC1. Our results reveal that somatic mutations such as T304I in Polβ impact critical protein–protein interactions, altering the stability and sub-cellular localization of Polβ and providing mechanistic insight into how key protein–protein interactions regulate cellular responses to stress.

scholarly journals The Anti-Oxidation and Mechanism of Essential Oil of Paederia scandens in the NAFLD Model of Chicken

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 850
Author(s):  
Qiang Wu ◽  
Huaqiao Tang ◽  
Hongbin Wang
Keyword(s):  
Oxidative Stress ◽  
Essential Oil ◽  
Protein Interactions ◽  
High Capacity ◽  
Protein Protein Interactions ◽  
Oxidation Activity ◽  
Alcoholic Fatty Liver ◽  
Differential Proteins ◽  
Paederia Scandens ◽  
Alcoholic Fatty Liver Disease

The aim of the study is to determine the underlying pathogenic mechanisms of oxidative stress and detect the anti-oxidative target of essential oil of Paederia scandens in non-alcoholic fatty liver disease (NAFLD). Chicken NAFLD was modeled by feeding with a high-capacity diet and Paederia scandens essential oil was used to treat the disease. The levels of hepatic reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and the differential proteins and network of protein–protein interactions were investigated in model and drug-treated groups. The results showed that essential oil of Paederia scandens down regulated the hepatic ROS and MDA level significantly (p < 0.05 and 0.01, respectively). The heat shock cognate 71 kDa protein (HSP7C) was down regulated significantly, which was in the center of the network and interacted with 22 other proteins. The results showed that oxidative stress played an important role in the pathogenesis of chicken NAFLD. The essential oil of Paederia scandens showed good anti-oxidation activity by down regulating the HSP7C protein, which can be used as a potential therapeutic target in chicken NAFLD.

scholarly journals Ceruloplasmin-derived peptide is the strongest regulator of oxidative stress and leukotriene synthesis in neutrophils

2017 ◽  
Vol 95 (3) ◽  
pp. 445-449 ◽  
Author(s):  
Ekaterina A. Golenkina ◽  
Alexey D. Livenskyi ◽  
Galina M. Viryasova ◽  
Yulia M. Romanova ◽  
Galina F. Sud’ina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory Function ◽  
Protein Protein Interactions ◽  
Synthesis Inhibitor ◽  
Strong Inhibitor ◽  
Serovar Typhimurium ◽  
P2 Peptide

Ceruloplasmin, an acute-phase protein, can affect the activity of leukocytes through its various enzymatic activities and protein–protein interactions (with lactoferrin, myeloperoxidase, eosinophil peroxidase, serprocidins, and 5-lipoxygenase (5-LOX), among others). However, the molecular mechanisms of ceruloplasmin activity are not clearly understood. In this study, we tested the ability of two synthetic peptides, RPYLKVFNPR (883–892) (P1) and RRPYLKVFNPRR (882–893) (P2), corresponding to the indicated fragments of the ceruloplasmin sequence, to affect neutrophil activation. Leukotriene (LT) B4 is the primary eicosanoid product of polymorphonuclear leukocytes (PMNLs, neutrophils). We studied leukotriene synthesis in PMNLs upon interaction with Salmonella enterica serovar Typhimurium. Priming of neutrophils with phorbol 12-myristate 13-acetate (PMA) elicited the strong regulatory function of P2 peptide as a superoxide formation inducer and leukotriene synthesis inhibitor. Ceruloplasmin-derived P2 peptide appeared to be a strong inhibitor of 5-LOX product synthesis under conditions of oxidative stress.

scholarly journals YBP1 and Its Homologue YBP2/YBH1 Influence Oxidative-Stress Tolerance by Nonidentical Mechanisms in Saccharomyces cerevisiae

2004 ◽  
Vol 3 (2) ◽  
pp. 318-330 ◽  
Author(s):  
Kailash Gulshan ◽  
Sherry A. Rovinsky ◽  
W. Scott Moye-Rowley
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Protein Interactions ◽  
Nuclear Accumulation ◽  
Protein Protein Interactions ◽  
Homologous Proteins ◽  
Oxidative Stresses ◽  
Double Mutant Strain ◽  
Biochemical Analyses

ABSTRACT In the yeast Saccharomyces cerevisiae, the transcription factor Yap1p is a central determinant of resistance to oxidative stress. Previous work has demonstrated that Yap1p is recruited from the cytoplasm to the nucleus upon exposure to the oxidants diamide and H2O2 in a process that requires the transient covalent linkage of the glutathione peroxidase Gpx3p to Yap1p. Genetic and biochemical analyses indicate that while both oxidants trigger nuclear accumulation of Yap1p, the function and regulation of this transcription factor is different under these two different oxidative stresses. Ybp1p (Yap1p-binding protein) has recently been demonstrated to be required for Yap1p-mediated H2O2 resistance but not diamide resistance. A Ybp1p homologous protein (Ybh1p/Ybp2p) was also detected in the S. cerevisiae genome. Here we compare the actions of these two closely related proteins and provide evidence that while both factors influence H2O2 tolerance, they do so by nonidentical mechanisms. A double mutant strain lacking both YBP1 and YBH1 genes is more sensitive to H2O2 and more defective in activation of Yap1p-dependent gene expression than either single mutant. Ybp1p has a more pronounced effect on these phenotypes than does Ybh1p. Protein-protein interactions between Yap1p and Ybp1p could be detected by either the yeast two-hybrid or coimmunoprecipitation approach while neither technique could demonstrate Yap1p-Ybh1p interactions. Overexpression experiments indicated that high levels of Ybh1p but not Ybp1p could bypass the H2O2 hypersensitivity of a gpx3Δ strain. Together, these data argue that these two homologous proteins act as parallel positive regulators of H2O2 tolerance.

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