A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells

Kim, Hyoung Kyu; Cho, Sung Woo; Heo, Hye Jin; Jeong, Sang Hoon; Kim, Min; Ko, Kyung Soo; Rhee, Byoung Doo; Mishchenko, Natalia P.; Васильева, Е. А.; Fedoreyev, Sergey A.; Stonik, Valentin A.; Han, Jin

doi:10.3390/md16060192

Cited by 20 publications

(17 citation statements)

References 35 publications

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“…The antimicrobial mechanism of echinochrome has not been completely resolved, but evidence suggests its production of hydrogen peroxide and/or iron chelation, abates microbial proliferation, ( Coates et al, 2018 ; Lebedev et al, 2005 ; Perry and Epel, 1981 ). All of these studies agree that sea urchin pigments have anti-microbial activity, and that these small molecules may also contribute to states of cell physiology and gene expression ( Jeong et al, 2014 ; Kim et al, 2018 ).…”

Section: Introductionmentioning

confidence: 60%

Regulation of dynamic pigment cell states at single-cell resolution

Perillo

Oulhen

Foster

et al. 2020

eLife

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Cells bearing pigment have diverse roles and are often under strict evolutionary selection. Here, we explore the regulation of pigmented cells in the purple sea urchin Strongylocentrotus purpuratus, an emerging model for diverse pigment function. We took advantage of single cell RNA-seq (scRNAseq) technology and discovered that pigment cells in the embryo segregated into two distinct populations, a mitotic cluster and a post-mitotic cluster. Gcm is essential for expression of several genes important for pigment function, but is only transiently expressed in these cells. We discovered unique genes expressed by pigment cells and test their expression with double fluorescence in situ hybridization. These genes include new members of the fmo family that are expressed selectively in pigment cells of the embryonic and in the coelomic cells of the adult - both cell-types having immune functions. Overall, this study identifies nodes of molecular intersection ripe for change by selective evolutionary pressures.

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Section: Introductionmentioning

confidence: 60%

Regulation of dynamic pigment cell states at single-cell resolution

Perillo

Oulhen

Foster

et al. 2020

eLife

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“…They investigated the potential use of Echinochrome A as an aPKC specific inhibitor and found that IC 50 for PKC-ι is 107 μM under in-vitro kinase assay conditions. Molecular docking simulation results suggested a direct binding of Echinochrome A with PKC-ι [89].…”

Section: Author Detailsmentioning

confidence: 96%

Atypical Protein Kinase Cs in Melanoma Progression

Ratnayake¹,

Apostolatos²,

Acevedo‐Duncan³

2019

Cutaneous Melanoma [Working Title]

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Melanoma is one of the fastest growing types of cancer worldwide in terms of incidence. To date, reports show over 92,000 new cases in the United States in 2018. Previously, we introduced protein kinase C-iota (PKC-ι) as an oncogene in melanoma. PKC-ι promotes survival and cancer progression along with PKCzeta(ζ). In addition, we reported that PKC-ι induced metastasis of melanoma cells by increasing Vimentin dynamics. Our previous results showed that PKC-ι inhibition downregulated epithelial-mesenchymal transition (EMT), while inducing apoptosis. In this chapter, we summarized these findings which were based on the in-vitro applications of five specific atypical PKC (aPKC) inhibitors. In addition, the underlying mechanisms of the transcriptional regulation of PRKCI gene expression in melanoma is also discussed. Results demonstrated that c-Jun promotes PRKCI expression along with Interleukin (IL)-6/8. Furthermore, forkhead box protein O1 (FOXO1) acts as a downregulator of PRKCI expression upon stimulation of IL-17E and intercellular adhesion molecule 1 (ICAM-1) in melanoma cells. Overall, the chapter summarizes the importance of PKC-ι/ζ in the progression of melanoma and discusses the cellular signaling pathways that are altered upon inhibitor applications. Finally, we established that aPKCs are effective novel biomarkers for use in the design of novel targeted therapeutics for melanoma.

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“…Echinochrome A, a naphthoquinoid pigment from sea urchins [157] that inhibits PKCɩ promoted mouse embryonic stem cells differentiation into cardiomyocytes [158]. In vitro kinase assays using echionochrome A also reported decreased activity of PKCδ (IC 50 = 107 μM).…”

Section: Atypical Pkcs As Therapeutic Targetmentioning

confidence: 99%

PKC and PKN in heart disease

Marrocco

Bogomolovas

Ehler³

et al. 2019

Journal of Molecular and Cellular Cardiology

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The protein kinase C (PKC) and closely related protein kinase N (PKN) families of serine/threonine protein kinases play crucial cellular roles. Both kinases belong to the AGC subfamily of protein kinases that also include the cAMP dependent protein kinase (PKA), protein kinase B (PKB/AKT), protein kinase G (PKG) and the ribosomal protein S6 kinase (S6K). Involvement of PKC family members in heart disease has been well documented over the years, as their activity and levels are mis-regulated in several pathological heart conditions, such as ischemia, diabetic cardiomyopathy, as well as hypertrophic or dilated cardiomyopathy. This review focuses on the regulation of PKCs and PKNs in different pathological heart conditions and on the influences that PKC/PKN activation has on several physiological processes. In addition, we discuss mechanisms by which PKCs and the closely related PKNs are activated and turned-off in hearts, how they regulate cardiac specific downstream targets and pathways, and how their inhibition by small molecules is explored as new therapeutic target to treat cardiomyopathies and heart failure.

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A Novel Atypical PKC-Iota Inhibitor, Echinochrome A, Enhances Cardiomyocyte Differentiation from Mouse Embryonic Stem Cells

Cited by 20 publications

References 35 publications

Regulation of dynamic pigment cell states at single-cell resolution

Regulation of dynamic pigment cell states at single-cell resolution

Atypical Protein Kinase Cs in Melanoma Progression

PKC and PKN in heart disease

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