Interaction of prostacyclin synthase with cytochromes P450

Gnedenko, O. V.; Yablokov, E. O.; Ершов, П. В.; Свирид, А. В.; Shkel, Tatsiana; Haidukevich, Irina; Strushkevich, Natallia; Gilep, Andrei A.; Usanov, Sergey A.; Иванов, А. С.

doi:10.18097/pbmc20196501063

Cited by 5 publications

(5 citation statements)

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“…CYB5D2 is a member of the progesterone membrane receptor-associated family and relies on the binding of heme to its cytochrome b5-like heme/steroid domain to exert biological activity ( 19 ). It is well known that CYB5D2 expression is downregulated in diverse cancers and act as tumor suppressors ( 8 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Expression of CYB5D2 expression is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer

Li¹,

Qiu²,

Chen³

et al. 2020

Transl Cancer Res TCR

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Background: CYB5D2 is a member of the membrane-associated progesterone receptors (MAPRs) family and plays essential roles in regulating nerve development. CYB5D2 is associated with tumor suppression in breast cancer. Despite the potential implication of CYB5D2 in cancer progression, its level and clinical significance in cervical cancer tissues has not been investigated yet. Via this study, we aimed to investigate the possible role played by CYB5D2 in epithelial-mesenchymal transition (EMT) in cervical cancer and correlate its level with clinical outcomes. Methods: The expressions of CYB5D2 and the EMT marker E-cadherin in different groups of cervical samples were compared using immunofluorescence. Furthermore, co-localization of CYB5D2 and E-cadherin was analyzed in different cervical tissue samples via confocal laser scanning microscopy. The relationship between CYB5D2/E-cadherin and the progression and clinicopathological features of cervical cancer were analyzed, and the prognostic value of CYB5D2 mRNA expression was evaluated in various tumors using the Kaplan-Meier plotter database. Results: CYB5D2 and E-cadherin were downregulated in cervical cancer (P<0.05). Co-localization of CYB5D2 and E-cadherin in cell cytoplasm in cervical cancer was apparent. The clinical and pathological information of patients with cervical cancer were analyzed, which revealed a statistically significant relationship between low CYB5D2 expression and the tumor FIGO stage (P<0.05). CYB5D2 expression was not correlated with tumors in terms of depth of myometrial invasion, patient age, histological type, and tumor grade (P>0.05). Higher expression levels of CYB5D2 mRNA were predicted to be associated with a better relapse-free survival (RFS) in patients with cervical cancer. E-cadherin expression was associated with invasive tumors, tumor grade, and FIGO stage (P<0.05) but not with patient age and histological type (P>0.05). There was a positive correlation between CYB5D2 and E-cadherin expression in cervical cancer (P<0.01).Conclusions: These results suggest that CYB5D2 acts as a tumor suppressor in cervical cancer, inhibiting EMT by hindering E-cadherin expression.

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Section: Discussionmentioning

confidence: 99%

Expression of CYB5D2 expression is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer

Li¹,

Qiu²,

Chen³

et al. 2020

Transl Cancer Res TCR

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“…Currently, surface plasmon resonance-based biosensors are widely used to study various interactions, including 1) protein-protein interaction [106,107]; 2) antigen-antibody interaction [108]; 3) protein-lipid interaction [109,110]; 4) low-molecular-weight ligand-protein interaction [111,112]; and 5) the influence of low-molecular-weight compounds on protein-protein interactions [113,114].…”

Section: Analysis Of the Interaction Of The Viral Antigen (D Antigen)...mentioning

confidence: 99%

Perspectives for the creation of a new type of vaccine preparations based on pseudovirus particles using polio vaccine as an example

Zhdanov,

Ivin,

Shishparenok

et al. 2023

BIOMED KHIM

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Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not optimal since they negatively affect the safety of the antigenic determinants of the inactivated particles and require additional purification stages. The most promising platforms for creating vaccines are based on pseudoviruses, i.e., viruses that have completely preserved the outer shell (capsid), while losing the ability to reproduce owing to the destruction of the genome. The irradiation of viruses with electron beam is the optimal way to create pseudoviral particles. In this review, with the example of the poliovirus, the main algorithms that can be applied to characterize pseudoviral particles functionally and structurally in the process of creating a vaccine preparation are presented. These algorithms are, namely, the analysis of the degree of genome destruction and coimmunogenicity. The structure of the poliovirus and methods of its inactivation are considered. Methods for assessing residual infectivity and immunogenicity are proposed for the functional characterization of pseudoviruses. Genome integrity analysis approaches, atomic force and electron microscopy, surface plasmon resonance, and bioelectrochemical methods are crucial to structural characterization of the pseudovirus particles.

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“…In previous publications, it was shown that both thromboxane and prostacyclin synthases had formed stable molecular complexes with a number of protein partners (Ershov et al, 2019a; Gnedenko et al, 2019; Svirid et al, 2017). Taken together, the SPR‐validated PPIs are shown schematically in Figure 1.…”

Section: Binary Ppis Involving Cyp5a1 and Cyp8a1mentioning

confidence: 99%

“…The phenomena of CYP/CYP hetero‐oligomerization is featured and well‐studied for many members of the cytochrome P450 superfamily, and it is believed to be associated with the modulating effect on the enzymatic reaction parameters of interacting cytochrome P450s (Bostick et al, 2016; Hazai & Kupfer, 2005; Reed & Backes, 2012). Hence, the complex formation between CYP5A1 (or CYP8A1) and microsomal CYPs (Gnedenko et al, 2019; Svirid et al, 2017) is obviously a particular case of CYP/CYP interactions described in the literature. Although it has been yet impossible to investigate the functional consequences of CYP5A1/CYP and CYP8A1/CYP hetero‐complexes, we can assume that such a modulation exists.…”

Section: Binary Ppis Involving Cyp5a1 and Cyp8a1mentioning

confidence: 99%

“…Although it has been yet impossible to investigate the functional consequences of CYP5A1/CYP and CYP8A1/CYP hetero‐complexes, we can assume that such a modulation exists. The interactions between synthases and some mitochondrial cytochrome P450 (CYP11A1, CYP11B1, and CYP11B2) (Gnedenko et al, 2019; Svirid et al, 2017) seemed to be rather surprising, but this effect was highly reproduced. It can be speculated that in this case, it deals with the conservatism of intermolecular interactions of CYPs, which are characteristic of the P450‐dependent monooxygenase system.…”

Section: Binary Ppis Involving Cyp5a1 and Cyp8a1mentioning

confidence: 99%

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A new insight into subinteractomes of functional antagonists: Thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases

Ершов

Yablokov

Zgoda

et al. 2021

Cell Biology International

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The current article aims to summarize all possible spectrum of protein–protein interactions for thromboxane A synthase (CYP5A1) and prostacyclin synthase (CYP8A1). These enzymes metabolize the same substrate (prostaglandin H2) and can participate in cardiovascular, inflammatory, immune processes, and apoptosis modulation, as well as significantly influence the risk of cancers. Binary protein–protein and multiprotein complexes are of great importance in enzyme‐regulating and signal‐transduction pathways. However, protein partners of CYP5A1 and CYP8A1 are not yet fully identified, although both synthases are considered as prospective drug targets. At least 36 novel protein partners of CYP5A1 and CYP8A1 were revealed from different tissue types using an approach based on affinity isolation and mass spectrometry. Enrichment analysis showed that these proteins have different molecular functions: folding (refolding), unfolded protein and chaperon binding, protein transport (export/import), posttranslational modification, protein domain‐specific binding, antioxidant activity, and glutathione homeostasis. A significant part of them, belonging to molecular chaperones, were common partners for CYP5A1 and CYP8A1, while other proteins were unique with the tissue‐dependent distribution. New aspects of CYP5A1 and CYP8A1 interactomics and hetero‐complex formation with different protein partners, including cytochrome P450s are discussed.

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Interaction of prostacyclin synthase with cytochromes P450

Cited by 5 publications

References 11 publications

Expression of CYB5D2 expression is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer

Expression of CYB5D2 expression is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer

Perspectives for the creation of a new type of vaccine preparations based on pseudovirus particles using polio vaccine as an example

A new insight into subinteractomes of functional antagonists: Thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases

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