Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis

Pitts, Michael R.; Hoffmann, Peter

doi:10.1016/j.ceca.2017.05.001

Cited by 124 publications

(91 citation statements)

References 122 publications

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“…In fact, application of DLTZ and THAP, L-type Ca 2+ channel and SERCA2a pump inhibitors, respectively, abolished the increase in contractility induced by PSELT. These observations are in agreement with previous studies showing the role of SELENOT as a regulator of Ca 2+ signaling and homeostasis in mammalian cells (Grumolato et al, 2008;Pitts and Hoffmann, 2018).…”

Section: Pselt As a Cardioactive Peptide In The Goldfishsupporting

confidence: 94%

Selenoprotein T as a new positive inotrope in the goldfish Carassius auratus

Mazza

Gattuso

Imbrogno

et al. 2019

Journal of Experimental Biology

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Selenoprotein T (SELENOT) is a thioredoxin-like protein, which mediates oxidoreductase functions via its redox active motif Cys-X-X-Sec. In mammals, SELENOT is expressed during ontogenesis and progressively decreases in adult tissues. In the heart, it is re-expressed after ischemia and induces cardioprotection against ischemia-reperfusion (IR) injury. SELENOT is present in teleost fish, including the goldfish Carassius auratus. This study aimed to evaluate the cardiac expression of SELENOT, and the effects of exogenous PSELT (a 43-52 SELENOT-derived peptide) on the heart function of C. auratus, a hypoxia tolerance fish model. We found that SELENOT was expressed in cardiac extracts of juvenile and adult fish, located in the sarcoplasmic reticulum (SR) together with calsequestrin-2. Expression increased under acute hypoxia. On ex vivo isolated and perfused goldfish heart preparations, under normoxia, PSELT dose dependently increased stroke volume (V S), cardiac output ð _ QÞ and stroke work (SW), involving cAMP, PKA, L-type calcium channels, SERCA2a pumps and pAkt. Under hypoxia, PSELT did not affect myocardial contractility. Only at higher concentrations (10 −8 to 10 −7 mol l −1) was an increase of V S and _ Q observed. It also reduced the cardiac expression of 3-NT, a tissue marker of nitrosative stress, which increases under low oxygen availability. These data are the first to propose SELENOT 43-52 (PSELT) as a cardiac modulator in fish, with a potential protective role under hypoxia.

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Section: Pselt As a Cardioactive Peptide In The Goldfishsupporting

confidence: 94%

Selenoprotein T as a new positive inotrope in the goldfish Carassius auratus

Mazza

Gattuso

Imbrogno

et al. 2019

Journal of Experimental Biology

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“…The biological function of the seven ER-resident selenoproteins, which include Seps1, is less well described. However, there is increasing interest in this group of selenoproteins due to their role in regulating oxidative and ER stress responses and intracellular calcium homeostasis (Arbogast and Ferreiro 2010;Shchedrina et al 2011;Yao et al 2013;Pitts and Hoffmann 2017;Addinsall et al 2018a). Here, we report for the first time that in skeletal muscle cells, that Seps1 expression is (Txnip) gene expression were measured in palmitateand vehicle-treated myoblasts transfected with the Seps1 siRNA or scramble control constructs.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of cellular stress responses by the endoplasmic reticulum-resident Selenoprotein S (Seps1) in proliferating myoblasts versus myotubes

et al. 2018

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The antioxidant Selenoprotein S (Seps1, Selenos) is an endoplasmic reticulum (ER)‐resident protein associated with metabolic and inflammatory disease. While Seps1 is highly expressed in skeletal muscle, its mechanistic role as an antioxidant in skeletal muscle cells is not well characterized. In C2C12 myotubes treated with palmitate for 24 h, endogenous Seps1 protein expression was upregulated twofold. Two different siRNA constructs were used to investigate whether decreased levels of Seps1 exacerbated lipid‐induced oxidative and ER stress in C2C12 myotubes and myoblasts, which differ with regards to cell cycle state and metabolic phenotype. In myoblasts, Seps1 protein knockdown of ~50% or ~75% exacerbated cellular stress responses in the presence of palmitate; as indicated by decreased cell viability and proliferation, higher H2O2 levels, a lower reduced to oxidized glutathione (GSH:GSSG) ratio, and enhanced gene expression of ER and oxidative stress markers. Even in the absence of palmitate, Seps1 knockdown increased oxidative stress in myoblasts. Whereas, in myotubes in the presence of palmitate, a ~50% knockdown of Seps1 was associated with a trend toward a marginal (3‐5%) decrease in viability (P = 0.05), decreased cellular ROS levels, and a reduced mRNA transcript abundance of the cellular stress marker thioredoxin inhibitory binding protein (Txnip). Furthermore, no enhancement of gene markers of ER stress was observed in palmitate‐treated myotubes in response to Seps1 knockdown. In conclusion, reduced Seps1 levels exacerbate nutrient‐induced cellular stress responses to a greater extent in glycolytic, proliferating myoblasts than in oxidative, differentiated myotubes, thus demonstrating the importance of cell phenotype to Seps1 function.

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“…The distinguishable feature of NFAT is that it relies on Ca 2+ influx and subsequent Ca 2+ /calmodulindependent phosphatase calcineurin to become dephosphorylated and being able to translocate to the nucleus to induce gene expression (43). Although VIMP has not yet been linked to the calcium signaling, other selenoproteins have been described to regulate the calcium signaling and homeostasis (44). We therefore further asked whether VIMP knockdown affects the calcium flux in Teffs and measured it by flow cytometry using the calcium indicator Indo-1.…”

Section: Vimp Controls Cytokine Expression Via the Ca 2+ /Nfatc2 Signmentioning

confidence: 99%

Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells

Capelle

Zeng

Danileviciute

et al. 2020

Preprint

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AbstractMany players regulating the CD4+ T cell-mediated inflammatory response have already been identified. However, the critical nodes that constitute the regulatory and signalling networks underlying CD4 T cell responses are still missing. Using a correlation network-guided strategy based on time-series transcriptome data of human CD4+CD25- effector T cells (Teffs), here we identified VIMP (VCP-interacting membrane protein), one of the 25 genes encoding selenocysteine in humans, as a gene regulating the effector functions of human CD4 T cells. Knocking-down VIMP in Teffs enhanced their proliferation and expression of several cytokines, including IL-2 and CSF2. We identified VIMP as an endogenous inhibitor of cytokine production in Teffs via both, the E2F5 transcription regulatory pathway and the Ca2+/NFATC2 signalling pathway. Our work not only indicates that VIMP might be a promising therapeutic target for various diseases involving CD4 T cells, but also shows that our network-guided approach might be generally applicable to different types of cells and can significantly aid in predicting new functions of the genes of interest.One-sentence summaryUsing a network-guided approach, we identified that Selenoprotein S (SELS or VIMP) negatively regulates cytokine expression of human CD4+ effector T cells via the E2F5 and calcium Ca2+/NFATC2 pathways.

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Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis

Cited by 124 publications

References 122 publications

Selenoprotein T as a new positive inotrope in the goldfish Carassius auratus

Selenoprotein T as a new positive inotrope in the goldfish Carassius auratus

Differential regulation of cellular stress responses by the endoplasmic reticulum-resident Selenoprotein S (Seps1) in proliferating myoblasts versus myotubes

Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells

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