L'implant cochléaire (résultats fonctionnels chez l'adulte. A propos de 35 patients.)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Novel svVEGF isoforms from Macrovipera lebetina venom interact with neuropilins.

International audienceIncreased vascular permeability and vasodilation are responses usually elicited by snake envenomation. In this report, we isolated from Macroviperalebetina venom two protein groups designated IC1 (Increasing Capillary1) and IC2 based on their activities on capillary permeability. Mass spectrometry analysis showed that IC1 contained four major proteins of 23,650, 24,306, 24,589 and 24,718Da, whereas IC2 contained three major proteins of 25,101, 25,194 and 25,298Da. N-terminal amino-acid sequencing revealed that IC1 and IC2 belong to the snake venom VEGF (svVEGF) family. IC1 and IC2 had a marked specificity for VEGFR-2, with affinities in the nanomolar range. Interestingly, they also bind to NRP1 and NRP2, with affinities in the micromolar range. This is the first report demonstrating that M. lebetina encodes several distinct svVEGFs, endowed with a capacity to interact with neuropilins. IC1 and IC2 could be valuable tools to understand the molecular properties of angiogenic factors and their receptors

Asteraceae Artemisia campestris and Artemisia herba-alba Essential Oils Trigger Apoptosis and Cell Cycle Arrest in Leishmania infantum Promastigotes

International audienceWe report the chemical composition and anti-Leishmania and antioxidant activity of Artemisia campestris L. and Artemisia herba-alba Asso. essential oils (EOs). Our results showed that these extracts exhibit different antioxidant activities according to the used assay. The radical scavenging effects determined by DPPH assay were of IC 50 = 3.3 mg/mL and IC 50 = 9.1 mg/mL for Artemisia campestris and Artemisia herba-alba essential oils, respectively. However, antioxidant effects of both essential oils, determined by ferric-reducing antioxidant power (FRAP) assay, were in the same range (2.3 and 2.97 mg eq EDTA/g EO, resp.), while the Artemisia herba-alba essential oil showed highest chelating activity of Fe 2+ ions (27.48 mM Fe 2+). Interestingly, we showed that both EOs possess dose-dependent activity against Leishmania infantum promastigotes with IC 50 values of 68 í µí¼‡g/mL and 44 í µí¼‡g/mL for A. herba-alba and A. campestris, respectively. We reported, for the first time, that antileishmanial activity of both EOs was mediated by cell apoptosis induction and cell cycle arrest at the sub-G0/G1 phase. All our results showed that EOs from A. herba-alba and A. campestris plants are promising candidates as anti-Leishmania medicinal products

Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells

Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma

Cardioprotective effect of VEGF and venom VEGF-like protein in acute myocardial ischemia in mice: effect on mitochondrial function.

International audienceCoronary endothelial dysfunction is involved in cardiac ischemia-reperfusion (IR) injury. Vascular endothelial growth factor (VEGF) activates endothelial cells and exerts cardioprotective effects in isolated hearts. The recently discovered viper venom protein called increasing capillary permeability protein (ICPP) exerts VEGF-like effects in endothelial cells. We examined whether VEGF or ICPP can influence IR outcome in vivo in mice. Dosages of VEGF and ICPP were determined by preliminary blood pressure study. In IR, both the proteins administered intravenously at reperfusion reduced infarct size (IS) by 57% for VEGF and 52% for ICPP (P < 0.01). Pretreatment with a selective VEGFR2 receptor antagonist abolished the reduction in IS. VEGF and ICPP induced ERK phosphorylation in the myocardium. IR triggered mitochondrial pore opening and impaired mitochondrial respiratory function. These effects of IR were prevented by VEGF or ICPP, which increased mitochondrial calcium retention capacity by 37% compared with saline (P < 0.05) and improved mitochondrial respiratory function (by 71% and 65%, respectively for state 3, and 51% and 38% for state 4, P < 0.01 for VEGF). Thus, intravenous administration of VEGF or ICPP at reperfusion largely reduces IS in IR, through stimulation of VEGFR2 receptors. This effect is mediated, at least in part, by improvement of IR-induced mitochondrial dysfunction

Macrovipecetin, a C-type lectin from Macrovipera lebetina venom, inhibits proliferation migration and invasion of SK-MEL-28 human melanoma cells and enhances their sensitivity to cisplatin.

BACKGROUND The resistance of melanoma cells to cisplatin restricts its clinical use. Therefore, the search for novel tumor inhibitors and effective combination treatments that sensitize tumor cells to this drug are still needed. We purified macrovipecetin, a novel heterodimeric C-type lectin, from Macrovipera lebetina snake venom and investigated its anti-tumoral effect on its own or combined with cisplatin, in human melanoma cells. METHODS Biochemical characterization, in vitro cells assays such as viability, apoptosis, adhesion, migration, invasion, Western blotting and in silico analysis were used in this study. RESULTS Macrovipecetin decreased melanoma cell viability 100 times more than cisplatin. Interestingly, when combined with the drug, macrovipecetin enhanced the sensitivity of SK-MEL-28 cells by augmenting their apoptosis through increased expression of the apoptosis inducing factor (AIF) and activation of ERK1/2, p38, AKT and NF-κB. Moreover, macrovipecetin alone or combined with cisplatin induced the expression of TRADD, p53, Bax, Bim and Bad and down-regulated the Bcl-2 expression and ROS levels in SK-MEL-28 cells. Interestingly, these treatments impaired SK-MEL-28 cell adhesion, migration and invasion through modulating the function and expression of αvβ3 integrin along with regulating E-cadherin, vimentin, β-catenin, c-Src and RhoA expression. In silico study suggested that only the α chain of macrovipecetin interacts with a region overlapping the RGD motif binding site on this integrin. CONCLUSIONS We validated the antitumor effect of macrovipecetin when combined, or not, with cisplatin on SK-MEL-28 cells. GENERAL SIGNIFICANCE The presented work proposes the potential use of macrovipecetin and cisplatin in combination as an effective anti-melanoma treatment