Nitric-oxide synthase trafficking inducer is a pleiotropic regulator of endothelial cell function and signaling

Chakraborty, Shreeta; Ain, Rupasri

doi:10.1074/jbc.m116.742627

Cited by 46 publications

(44 citation statements)

References 76 publications

(81 reference statements)

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“…Of the EDE proteins expected to show differences between patients with CeVD and control subjects, only eNOS did not distinguish control subjects from patients with CeVD (Table 1). In contrast, EDE levels of NOSTRIN (13) were significantly higher in patients with CeVD than in control subjects (Supplemental Fig. 1), suggesting a greater redistribution of eNOS from plasma membrane to cytoplasmic vesicles with resultant attenuation of NO production in CeVD endothelium.…”

Section: Resultsmentioning

confidence: 90%

Altered cargo proteins of human plasma endothelial cell–derived exosomes in atherosclerotic cerebrovascular disease

et al. 2017

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Plasma endothelial cell-derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycoprotein VI. EDE levels of VCAM-1, von Willebrand factor, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, and lysyl oxidase-2 and the cerebrovascularselective proteins glucose transporter 1, permeability-glycoprotein, and large neutral amino acid transporter 1 were significantly higher for 18 patients with cerebrovascular disease (CeVD) than for 18 age-and gender-matched control subjects. PDE levels of PDGF-AA, platelet glycoprotein VI, integrin-linked kinase-1, high mobility group box-1 protein, chemokine CXCL4, and thrombospondin-1 were significantly higher in patients with CeVD than in control subjects, but differences were less with greater overlaps than for EDE proteins. EDE levels of Yes-associated protein (YAP) were higher and of P(S127)-YAP lower in patients with CeVD than in control subjects, consistent with heightened activity of this mechanical force-sensitive system in atherosclerosis. Elevated EDE and PDE levels of atherosclerosis-promoting proteins in CeVD justify clinical studies of their potential value as biomarkers.-Goetzl, E. J., Schwartz, J. B., Mustapic, M., Lobach, I. V., Daneman, R., Abner, E. L., Jicha, G. A. Altered cargo proteins of human plasma endothelial cell-derived exosomes in atherosclerotic cerebrovascular disease. FASEB J. 31, 3689-3694 (2017). www.fasebj.org

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Section: Resultsmentioning

confidence: 90%

Altered cargo proteins of human plasma endothelial cell–derived exosomes in atherosclerotic cerebrovascular disease

et al. 2017

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“…Western blotting was performed as described previously 61 . Total protein was extracted from tissue or cells using RIPA buffer.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA regulation of Transthyretin in trophoblast differentiation and Intra-Uterine Growth Restriction

Saha

Chakraborty

Bhattacharya

et al. 2017

Sci Rep

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Placental trophoblast cells produce various cytokines, transporters vital to normal embryogenesis. Transthyretin (TTR) aids trans-placental passage of maternal thyroxin (TH) to fetal circulation. Inadequate TH delivery leads to developmental abnormality. Regulation of TTR biosynthesis in placenta is critical for normal embryo development. We showed here that TTR transcripts were expressed more in fetal placenta. Using bioinformatic analysis and confirmation with dual-luciferase reporter assays, we found that miR-200a-3p and miR-141-3p inhibited TTR expression by directly binding to the 3′UTR of TTR, which is reversed by mutation in the microRNA binding site. Differentiation of human trophoblast BeWo cells was associated with decreased TTR transcript and protein levels with concomitant increase in the levels of both microRNAs. Interestingly, ectopic overexpression of the microRNA mimics abrogated thyroxin uptake by BeWo cells, which was reversed by the corresponding inhibitors. Furthermore, in a rat model of intra-uterine growth restriction (IUGR), TTR expression decreased significantly in placenta with reciprocal rise in miR-141-3p but not 200a-3p. In human IUGR placenta, TTR transcript and protein levels were significantly lower associated with high expression of miR-141-3p but not 200a-3p. These data provides new insight into physiological role of miR-141-3p in regulating TTR during trophoblast differentiation and IUGR.

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“…Several mediators contribute to angiogenesis during tumor development, including cytokines and chemokines [ 33 ], reactive oxygen species (ROS) [ 34 ] and NO [ 35 ]. IL-1β is produced by inflammatory cells and, together with TNF-α, INF-γ and IL-18, activate macrophages and neutrophils for phagocytosis and release of reactive oxygen and nitrogen species [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

Santos

Brito

Ferreira

et al. 2018

IJMS

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Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µg/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1β, TNF-α, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.

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Nitric-oxide synthase trafficking inducer is a pleiotropic regulator of endothelial cell function and signaling

Cited by 46 publications

References 76 publications

Altered cargo proteins of human plasma endothelial cell–derived exosomes in atherosclerotic cerebrovascular disease

Altered cargo proteins of human plasma endothelial cell–derived exosomes in atherosclerotic cerebrovascular disease

MicroRNA regulation of Transthyretin in trophoblast differentiation and Intra-Uterine Growth Restriction

Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

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