Alterations in the placental proteome in association with the presence of black carbon particles: A discovery study.

Background: Exposure to ambient air pollution is known to cause direct and indirect molecular expression changes in the placenta, on the DNA, mRNA, and protein levels. Ambient black carbon (BC) particles can be found in the human placenta already very early in gestation. However, the effect of in utero BC exposure on the entire placental proteome has never been studied to date.

New Pathophysiological Insights from Serum Proteome Profiling in Equine Atypical Myopathy.

Equine atypical myopathy (AM) is a severe environmental intoxication linked to the ingestion of protoxins contained in seeds and seedlings of the sycamore maple () in Europe. The toxic metabolites cause a frequently fatal rhabdomyolysis syndrome in grazing horses. Since these toxic metabolites can also be present in cograzing horses, it is still unclear as to why, in a similar environmental context, some horses show signs of AM, whereas others remain clinically healthy.

Indacaterol inhibits collective cell migration and IGDQ-mediated single cell migration in metastatic breast cancer MDA-MB-231 cells.

Metastasis is the main cause of deaths related to breast cancer. This is particular the case for triple negative breast cancer. No targeted therapies are reported as efficient until now.

The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation.

Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation at both the global and the transcript-specific levels. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during exit from pluripotency and is then globally repressed during later steps of hepatogenic maturation.

Senescence Induced by UVB in Keratinocytes Impairs Amino Acids Balance.

Skin is one of the most exposed organs to external stress. Namely, UV rays are the most harmful stress that could induce important damage leading to skin aging and cancers. At the cellular level, senescence is observed in several skin cell types and contributes to skin aging.

DNA repair during nonreductional meiosis in the asexual rotifer .

Rotifers of the class Bdelloidea are microscopic animals notorious for their long-term persistence in the apparent absence of sexual reproduction and meiotic recombination. This evolutionary paradox is often counterbalanced by invoking their ability to repair environmentally induced genome breakage. By studying the dynamics of DNA damage response in the bdelloid species , we found that it occurs rapidly in the soma, producing a partially reassembled genome.

Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model.

Background: Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis.

IGDQ motogenic peptide gradient induces directional cell migration through integrin (αv)β3 activation in MDA-MB-231 metastatic breast cancer cells.

In the context of breast cancer metastasis study, we have shown in an in vitro model of cell migration that IGDQ-exposing (IsoLeu-Gly-Asp-Glutamine type I Fibronectin motif) monolayers (SAMs) on gold sustain the adhesion of breast cancer MDA-MB-231 cells by triggering Focal Adhesion Kinase and integrin activation. Such tunable scaffolds are used to mimic the tumor extracellular environment, inducing and controlling cell migration. The observed migratory behavior induced by the IGDQ-bearing peptide gradient along the surface allows to separate cell subpopulations with a "stationary" or "migratory" phenotype.

Taking Advantage of the Senescence-Promoting Effect of Olaparib after X-ray and Proton Irradiation Using the Senolytic Drug, ABT-263.

Radiotherapy (RT) is a key component of cancer treatment. Although improvements have been made over the years, radioresistance remains a challenge. For this reason, a better understanding of cell fates in response to RT could improve therapeutic options to enhance cell death and reduce adverse effects.

Priming of mesenchymal stem cells with a hydrosoluble form of curcumin allows keeping their mesenchymal properties for cell-based therapy development.

Mesenchymal stem cells are increasingly studied for their use as drug-carrier in addition to their intrinsic potential for regenerative medicine. They could be used to transport molecules with a poor bioavailability such as curcumin in order to improve their clinical usage. This natural polyphenol, well-known for its antioxidant and anti-inflammatory properties, has a poor solubility that limits its clinical potential.

Optimization of label-free nano LC-MS/MS analysis of the placental proteome.

The placenta can be regarded as a mirror of the events to which the fetus is exposed during development. The placental proteome has been studied with several methodologies differing in sample handling, protein extraction, and processing. We optimized a protocol to analyze the placental proteome by means of label-free nano-LC-MS/MS mass spectrometry with regard to sample treatment, protein extraction, and protein digestion, in order to obtain a high protein concentration for identification of a specific protein signature according to the conditions studied.

Cycling hypoxia promotes a pro-inflammatory phenotype in macrophages via JNK/p65 signaling pathway.

Cycling hypoxia (cyH), also called intermittent hypoxia, occurs in solid tumors and affects different cell types in the tumor microenvironment and in particular the tumor-associated macrophages (TAMs). As cyH and TAMs both favor tumor progression, we investigated whether cyH could drive the pro-tumoral phenotype of macrophages. Here, the effects of cyH on human THP-1 macrophages and murine bone marrow-derived macrophages (BMDM), either unpolarized M0, or polarized in M1 or M2 phenotype were studied.

Characterization of the role of TMEM45A in cancer cell sensitivity to cisplatin.

TMEM45A is a transmembrane protein involved in tumor progression and cancer resistance to chemotherapeutic agents in hypoxic condition. It is correlated to a low breast cancer patient overall survival. However, little is known about this protein, in particular the mechanisms by which TMEM45A modulates cancer cell chemosensitivity.

Proton irradiation orchestrates macrophage reprogramming through NFκB signaling.

Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This phenotype contrasts with the M1-like macrophages, which exhibits proinflammatory, phagocytic, and antitumoral functions.

The Transcription Factor 7-Like 2-Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation.

Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remains poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7-like 2 (TCF7L2) (a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS.

Proteomic Study of SUMOylation During Solanum tuberosum-Phytophthora infestans Interactions.

Invasive plant pathogens have developed the ability to modify the metabolism of their host, promoting metabolic processes that facilitate the growth of the pathogen at the general expense of the host. The particular enzymatic process SUMOylation, which performs posttranslational modification of target proteins, leading to changes in many aspects of protein activity and, hence, metabolism, has been demonstrated to be active in many eukaryotic organisms, both animals and plants. Here, we provide experimental evidence that indicates that, in leaves of Solanum tuberosum that have been infected by Phytophthora infestans, the SUMO (small ubiquitin-like modifier) pathway enzymes of the host are partially under transcriptional control exerted by the oomycete.

Proteomics analysis of the endogenous, constitutive, leaf SUMOylome.

Unlabelled: SUMOylation is a post-translational modification which regulates a number of critical biological processes in, for example mammals, yeast and plants. In order to fully understand the functional effects of SUMOylation an essential first step is the identification of endogenous targets for SUMOylation. Here we report the results of using a recently developed proteomic approach based on the use of 3D gels to identify the endogenous SUMO targets in leaves of Solanum tuberosum.

Effects of a Sublethal and Transient Stress of the Endoplasmic Reticulum on the Mitochondrial Population.

Endoplasmic reticulum (ER) and mitochondria are not discrete intracellular organelles but establish close physical and functional interactions involved in several biological processes including mitochondrial bioenergetics, calcium homeostasis, lipid synthesis, and the regulation of apoptotic cell death pathways. As many cell types might face a transient and sublethal ER stress during their lifetime, it is thus likely that the adaptive UPR response might affect the mitochondrial population. The aim of this work was to study the putative effects of a non-lethal and transient endoplasmic reticulum stress on the mitochondrial population in HepG2 cells.

Copper(II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response.

The potential toxic effects of two types of copper(II) oxide (CuO) nanoparticles (NPs) with different specific surface areas, different shapes (rod or spheric), different sizes as raw materials and similar hydrodynamic diameter in suspension were studied on human hepatocarcinoma HepG2 cells. Both CuO NPs were shown to be able to enter into HepG2 cells and induce cellular toxicity by generating reactive oxygen species. CuO NPs increased the abundance of several transcripts coding for pro-inflammatory interleukins and chemokines.

Hypersensitivity of mtDNA-depleted cells to staurosporine-induced apoptosis: roles of Bcl-2 downregulation and cathepsin B.

We show that mitochondrial DNA (mtDNA)-depleted 143B cells are hypersensitive to staurosporine-induced cell death as evidenced by a more pronounced DNA fragmentation, a stronger activation of caspase-3, an enhanced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, and a more dramatic cytosolic release of cytochrome c. We also show that B-cell CLL/lymphoma-2 (Bcl-2), B-cell lymphoma extra large (Bcl-X(L)), and myeloid cell leukemia-1 (Mcl-1) are constitutively less abundant in mtDNA-depleted cells, that the inhibition of Bcl-2 and Bcl-X(L) can sensitize the parental cell line to staurosporine-induced apoptosis, and that overexpression of Bcl-2 or Bcl-X(L) can prevent the activation of caspase-3 in ρ(0)143B cells treated with staurosporine. Moreover, the inactivation of cathepsin B with CA074-Me significantly reduced cytochrome c release, caspase-3 activation, PARP-1 cleavage, and DNA fragmentation in mtDNA-depleted cells, whereas the pan-caspase inhibitor failed to completely prevent PARP-1 cleavage and DNA fragmentation in these cells, suggesting that caspase-independent mechanisms are responsible for cell death even if caspases are activated.

Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor.

Background: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a) and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence.

Methodology/principal Findings: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival.

Identification of DH IC-2 as a HIF-1 independent protein involved in the adaptive response to hypoxia in tumor cells: A putative role in metastasis.

The master regulator of the adaptive response to hypoxia is HIF-1. However, while some data show that HIF-1 can control more than 80% of the genes induced under hypoxia, other experiments clearly demonstrate that a part of the hypoxic response is independent of HIF-1. The goal of this study was to identify some of these HIF-1 independent factors and to investigate their functional role in the adaptation of tumor cells to hypoxia.

Repeated exposures to UVB induce differentiation rather than senescence of human keratinocytes lacking p16(INK-4A).

Skin cancers and extrinsic aging are delayed consequences of cumulative UV radiation insults. Exposure of human keratinocytes to UVB has been previously shown to trigger premature senescence. In order to explore the involvement of the cyclin-dependent kinase inhibitor p16(INK-4a) in UVB-induced premature senescence, we developed an original model of repeated sublethal exposures of human keratinocytes deficient in p16(INK-4a).

Increased abundance of cytoplasmic and nuclear caveolin 1 in human diploid fibroblasts in H(2)O(2)-induced premature senescence and interplay with p38alpha(MAPK).

Treatment of IMR-90 human diploid fibroblasts with a sublethal concentration of H(2)O(2) induces premature senescence. We investigated the protein abundance, subcellular localization and involvement of caveolin 1 in premature senescence. Caveolin 1 is a scaffolding protein able to concentrate and organize signaling molecules within the caveolae membrane domains.