Immediate early inflammatory gene responses of human umbilical vein endothelial cells to hemorrhagic venom

Albrecht, Eric A.; Dhanasekaran, Saravana M.; Tomlins, Scott A.

doi:10.1007/s00011-010-0286-1

Cited by 6 publications

(7 citation statements)

References 36 publications

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“…Endothelial expression of MT2A has been described by others [19,20], while MT3 expression was suggested to be restricted to the brain and male reproductive organs [21]. Here, we show that MT3 mRNA is expressed by EC as well, albeit indeed at low levels.…”

Section: Discussionsupporting

confidence: 75%

Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells

et al. 2014

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Metallothioneins (MTs) are small cysteine-rich proteins which are involved in e.g. metal homeostasis, metal detoxification and protection against oxidative stress. In addition, several MTs have been shown to regulate expression of proangiogenic growth factors like vascular endothelial growth factor. Detailed information about the expression and regulation of specific MT isoforms in endothelial cells (EC) is limited. We therefore performed extensive mRNA expression profiling of all known human MTs in EC. We found that the basal endothelial expression is restricted to MT1E, MT1X, MT2A, and MT3. Physiological activation of EC by exposure to serum increased the expression of MT1E and MT2A and induced the expression of MT1M. Furthermore, exposure to zinc or copper induced the expression of most MT1 isoforms, while hypoxia specifically increased the expression of MT1E, MT1M, MT1X, and MT3. Finally, knockdown of the dominant MT isoform in EC, i.e. MT2A, resulted in decreased proliferation and sprouting as well as in increased migration of human umbilical vein EC. Together, these findings provide a link between MTs and angiogenesis.

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Section: Discussionsupporting

confidence: 75%

Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells

et al. 2014

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“…The discovery of the protein association between EOLA1 and metallothionein 2A (MT2A) has been confirmed by yeast double-hybridization and coimmunoprecipitation assay [ 2 , 5 ]. MT2A is known to have anti-inflammatory, antiendotoxin, and tumor-inhibiting effects in cell cultures [ 6 , 7 ]. In addition, MT2A inhibits cell growth through the induction of apoptosis and G2/M arrest, which negatively regulates NF- κ B pathway by upregulation of I κ B- α and downregulation of p-I κ B- α and cyclin D1 [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells

Leng

Lei

Meng

et al. 2015

International Journal of Inflammation

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Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells.

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“…Those activities may contribute to activation of apoptosis- and inflammatory-related pathways through the generation of ROS. In this regard, the venom from another Viperidae, Echis carinatus , induced an overexpression of genes associated to ROS pathways, including the cytochrome P450 enzymes, in HUVECs (human umbilical vein endothelial cells) [ 66 ]. Additionally, B. jararaca and Crotalus atrox venoms induced a significant increase in the expression of genes related to apoptosis and inflammatory pathways in HUVECs [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

Nicolau

Prorock

Bao

et al. 2018

Toxins

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Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

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Immediate early inflammatory gene responses of human umbilical vein endothelial cells to hemorrhagic venom

Abstract: These data suggest that acute vascular injury induced by hemorrhagic snake venom initiates an anti-oxidant response primarily involving metallothioneins.

Cited by 6 publications

References 36 publications

Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells

Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells

EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

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