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Jamie J L Williams, Nasser Alotaiq, William Mullen, Richard Burchmore, Libin Liu, George S Baillie, Fred Schaper, Paul F Pilch, Timothy M Palmer
Effective suppression of JAK-STAT signalling by the inducible inhibitor "suppressor of cytokine signalling 3" (SOCS3) is essential for limiting signalling from cytokine receptors. Here we show that cavin-1, a component of caveolae, is a functionally significant SOCS3-interacting protein. Biochemical and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins, thereby reducing caveola abundance in endothelial cells...
January 12, 2018: Nature Communications
Yan Willière, Aljona Borschewski, Andreas Patzak, Tatiana Nikitina, Carsten Dittmayer, Anna L Daigeler, Markus Schuelke, Sebastian Bachmann, Kerim Mutig
Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known about their functional role in the kidney. We tested the hypothesis that caveolae modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient (Cav1-/-) mice were studied. Cav1 expression and caveolae formation were present in vascular cells, late distal convoluted tubule and principal connecting tubule and collecting duct cells of WT but not Cav1-/- kidneys. Urinary sodium excretion was increased by 94% and urine flow by 126% in Cav1-/- mice (p < 0...
January 11, 2018: Scientific Reports
Xiaoyou Qu, Yang Zou, Chuyu He, Yuanhang Zhou, Yao Jin, Yunqiang Deng, Ziqi Wang, Xinru Li, Yanxia Zhou, Yan Liu
To ensure that antitumor drugs can be effectively transported across intestinal barrier and then quickly released in tumor cells, mixed polymeric micelles (Mix-PMs) were designed and fabricated by combining poly(2-ethyl-2-oxazoline)-vitamin E succinate (PEOz-VES) with TPGS1000 for enhancing intestinal absorption of paclitaxel. PEOz-VES exhibited an extremely low critical micelle concentration and negligible cytotoxicity. The Mix-PMs were characterized to have about 20 nm in diameter, uniform spherical morphology, high drug-loading content and sustained drug release profile with a retained pH-sensitivity...
November 2018: Drug Delivery
Sayo Horibe, Toshihito Tanahashi, Shoji Kawauchi, Yoshiki Murakami, Yoshiyuki Rikitake
BACKGROUND: Exosomes, small-membrane vesicles, are secreted by cells and include several types of proteins and nucleic acids. Exosomes transfer cellular information derived from donor cells and are involved in various physiological and pathological events, such as organ-specific metastasis. Elucidating the exosome uptake mechanisms is important for understanding the progression processes of organ-specific metastasis. However, whether the exosomes secreted by the donor cells are selectively or non-selectively incorporated into the recipient cells is unknown...
January 6, 2018: BMC Cancer
M R Plewes, P D Burns
Many receptors span the plasma membrane allowing for signal transduction, converting extracellular signals into intracellular signals. Following ligand-induced activation, membrane-bound receptors are taken into endocytic vesicles, where they are targeted for degradation or recycled back to the plasma membrane. The objectives of the present study were to determine the influence of fish oil on (1) PGF2α-induced receptor internalization and trafficking of the PGF2α (FP) receptor, (2) cytoskeletal structural integrity, and (3) PGF2α-induced mitogen-activated protein kinase (MAPK) signaling in bovine luteal cells...
December 12, 2017: Domestic Animal Endocrinology
Yi-Qun Li, Li Sun, Jun Li
Increasing evidence has demonstrated support for the endocytic capacities of teleost B cells. In the present study, the ability of turbot IgM+ B cells to ingest microspheres of different sizes and the corresponding internalization pathways were investigated. The results showed that IgM+ B cells exhibited relatively high endocytic capacities for 0.5 μm and 1 μm latex beads, and that different mechanisms were employed for IgM+ and IgM- cells to uptake 0.5 μm and 1 μm beads. For 0.5 μm beads, IgM+ B cells apparently employed macropinocytosis-dependent endocytic pathway, whereas IgM- cells utilized a different process involving both clathrin- and caveolae-mediated pathways...
January 2, 2018: Developmental and Comparative Immunology
Viviana Meraviglia, Patrizia Benzoni, Sara Landi, Carmen Murano, Marianna Langione, Benedetta M Motta, Serena Baratto, Rosamaria Silipigni, Marina Di Segni, Peter P Pramstaller, Dario DiFrancesco, Elisabetta Gazzerro, Andrea Barbuti, Alessandra Rossini
Caveolinopathies are a heterogeneous family of genetic pathologies arising from alterations of the caveolin-3 gene (CAV3), encoding for the isoform specifically constituting muscle caveolae. Here, by reprogramming peripheral blood mononuclear cells, we report the generation of induced pluripotent stem cells (iPSCs) from three patients carrying the ΔYTT deletion, T78K and W101C missense mutations in caveolin-3. iPSCs displayed normal karyotypes and all the features of pluripotent stem cells in terms of morphology, specific marker expression and ability to differentiate in vitro into the three germ layers...
December 18, 2017: Stem Cell Research
Nofrat Schwartz, Anjali Verma, Chandana Muktipaty, Caroline Bivens, Zvi Schwartz, Barbara D Boyan
There is growing evidence that laryngeal cancers are responsive to sex hormones, specifically 17β-estradiol (E2), despite controversy regarding the presence and characterization of E2 receptors (ER). Determination of sex hormone responsiveness impacts the prognosis of laryngeal cancer patients and the treatment modalities implemented by their clinicians. Discovery of membrane-associated steroid hormone receptors and rapid membrane signaling opened the possibility that cancers previously labeled 'non-hormone dependent' and 'ER negative' might in fact be susceptible to the effects of E2 via these membrane receptors...
December 20, 2017: Steroids
Alexandra Diana Vrapciu, Mugurel Constantin Rusu
Telocytes (TCs) are stromal cells with characteristic long, thin and moniliform prolongations termed telopodes. They were formerly termed interstitial Cajal-like cells. A characteristic set of markers to identify TCs in light microscopy has not been established until now. Transmission electron microscopy (TEM) is a better tool for identifying TCs. Telocytes display caveolae and can express caveolin-1. On the other hand, endothelial cells (ECs) as well as endothelial progenitor cells (EPCs) have caveolae. Recent evidence suggests that a subset of TCs are in fact EPCs...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Cecília Jacques Gonçalves de Almeida
Caveolins, encoded by the CAV gene family, are the main protein components of caveolae. In most tissues, caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are co-expressed, and Cav-2 targeting to caveolae depends on the formation of heterooligomers with Cav-1. Notwithstanding, Cav-2 has unpredictable activities, opposing Cav-1 in the regulation of some cellular processes. While the major roles of Cav-1 as a modulator of cell signaling in inflammatory processes and in immune responses have been extensively discussed elsewhere, the aim of this review is to focus on data revealing the distinct activity of Cav-1 and Cav-2, which suggest that these proteins act antagonistically to fine-tune a variety of cellular processes relevant to inflammation...
2017: Frontiers in Immunology
Naël Osmani, Julien Pontabry, Jordi Comelles, Nina Fekonja, Jacky G Goetz, Daniel Riveline, Elisabeth Georges-Labouesse, Michel Labouesse
Hemidesmosomes (HDs) are epithelial-specific cell-matrix adhesions, which stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly understood. Here we identify a pathway essential for HD remodeling, and outline its role with respect to α6β4 integrin recycling. We find that α6β4 integrin chains localize to the plasma membrane, caveolae and Arf6+ endocytic compartments...
December 13, 2017: Molecular Biology of the Cell
Mauricio A Lillo, Pablo S Gaete, Mariela Puebla, Nicolás M Ardiles, Inés Poblete, Alvaro Becerra, Felipe Simon, Xavier F Figueroa
Na+-Ca2+ exchanger (NCX) contributes to control the intracellular free Ca2+ concentration ([Ca2+]i), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca2+ uptake in the endothelium-dependent vasodilation of rat isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the acetylcholine (ACh)-induced vasodilation was abolished by treatment with the NCXrm blockers SEA0400, KB-R7943, or SN-6. Consistent with that, the ACh-induced hyperpolarization observed in primary cultures of mesenteric endothelial cells and in smooth muscle of isolated mesenteric resistance arteries was attenuated by KB-R7943 and SEA0400, respectively...
December 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Andrew Kuo, Monica Y Lee, Kui Yang, Richard W Gross, William C Sessa
Lipid droplets (LD) are dynamic organelles involved in intracellular lipid metabolism in almost all eukaryotic cells and LD associated proteins tightly regulate their dynamics. One LD coat proteins is caveolin-1 (Cav-1), an essential component for caveolae assembly in highly differentiated cells including adipocytes, smooth muscle cells and endothelial cells (EC). However, the role of Cav-1 in LD dynamics is unclear. Here, we report that EC lacking Cav-1 exhibit impaired LD formation. The decreased LD formation was due to due to enhanced  lipolysis, and not caused by reduced triglyceride synthesis or fatty acid uptake...
December 4, 2017: Journal of Biological Chemistry
Eric Seemann, Minxuan Sun, Sarah Krueger, Jessica Tröger, Wenya Hou, Natja Haag, Susann Schüler, Martin Westermann, Christian A Huebner, Bernd Romeike, Michael M Kessels, Britta Qualmann
Several human diseases are associated with a lack of caveolae. Yet, the functions of caveolae and the molecular mechanisms critical for shaping them still are debated. We show that muscle cells of syndapin III KO mice show severe reductions of caveolae reminiscent of human caveolinopathies. Yet, different from other mouse models, the levels of the plasma membrane-associated caveolar coat proteins caveolin3 and cavin1 were both not reduced upon syndapin III KO. This allowed for dissecting bona fide caveolar functions from those supported by mere caveolin presence and also demonstrated that neither caveolin3 nor caveolin3 and cavin1 are sufficient to form caveolae...
December 5, 2017: ELife
Christopher R Anderson, Yehou D M Gnopo, Filippo Gambinossi, Steven E Mylon, James K Ferri
Nanoparticle (NP) interactions with cellular systems are influenced by both NP physico-chemical properties and the presence of surface-bound proteins that are adsorbed in biological environments. Here, we characterize cellular responses to silver nanoparticles (AgNPs) functionalized with poly(MeO2 MAx -co-OEGMAy ) brushes with tunable hydrophobicity and explore how these responses are modulated by the presence or absence of serum proteins. Poly(MeO2 MAx -co-OEGMAy ) with variable composition (5-10% OEGMA) was fabricated to elicit differential hydrophobicity at 37°C for AgNPs capped with these copolymers...
November 30, 2017: Journal of Biomedical Materials Research. Part A
Xiaosa Li, Weiyu Chen, Ping Li, Jinzhi Wei, Yang Cheng, Pei Liu, Qing Yan, Xingyan Xu, Yuhong Cui, Zhengtian Gu, Tommaso Simoncini, Xiaodong Fu
Rationale: Postmenopausal atherosclerosis (AS) has for decades been attributed to estrogen deficiency. Although the follicular stimulating hormone (FSH) levels rise sharply in parallel, the direct effect of FSH on AS has never been investigated. In this study, we explored the possible role of FSH in the development of AS. Methods: This was a prospective cohort study of 48 healthy premenopausal and 15 postmenopausal women. ApoE knockout mice were used as atherosclerosis model and human umbilical vascular endothelial cells (HUVECs) were cultured as cell model...
2017: Theranostics
Tahmina Afroz, Yusuke Hiraku, Ning Ma, Sharif Ahmed, Shinji Oikawa, Shosuke Kawanishi, Mariko Murata
OBJECTIVES: Indium compounds are used in manufacturing displays of mobile phones and televisions. However, these materials cause interstitial pneumonia in exposed workers. Animal experiments demonstrated that indium compounds caused lung cancer. Chronic inflammation is considered to play a role in lung carcinogenesis and fibrosis induced by particulate matters. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed during inflammation and may participate in carcinogenesis. To clarify the mechanism of carcinogenesis, we examined 8-nitroG formation in indium-exposed cultured cells...
November 29, 2017: Journal of Occupational Health
Ihor Yakymovych, Mariya Yakymovych, Carl-Henrik Heldin
Transforming growth factor β (TGFβ) family members signal via heterotetrameric complexes of type I (TβRI) and type II (TβRII) dual specificity kinase receptors. The availability of the receptors on the cell surface is controlled by several mechanisms. Newly synthesized TβRI and TβRII are delivered from the Golgi apparatus to the cell surface via separate routes. On the cell surface, TGFβ receptors are distributed between different microdomains of the plasma membrane and can be internalized via clathrin- and caveolae-mediated endocytic mechanisms...
November 25, 2017: Acta Biochimica et Biophysica Sinica
Satomi Nadanaka, Hiroki Kinouchi, Hiroshi Kitagawa
Tumor metastasis involves cancer cell invasion across basement membranes and interstitial tissues. The initial invasion step consists of adherence of the tumor cell to the extracellular matrix (ECM), and this binding transduces a variety of signals from the ECM to the tumor cell. Accordingly, it is critical to establish the mechanisms by which extracellular cues influence the intracellular activities that regulate tumor cell invasion. Here, we found that invasion of the basal-like breast cancer cell line BT-549 is enhanced by the ECM component chondroitin sulfates (CSs)...
November 28, 2017: Journal of Biological Chemistry
Fan Deng, Shuang Wang, Shuyun Cai, Zhe Hu, Riping Xu, Jingjing Wang, Du Feng, Liangqing Zhang
Endothelial microvesicles (EMVs), released after endothelial cell (EC) apoptosis or activation, may carry many adverse signals and propagate injury by intercellular transmission. Caveolae are 50-100 nm cell surface plasma membrane invaginations involved in many pathophysiological processes. Recent evidence has indicated EMVs and caveolae may have functional effects in cells undergoing H/R injury. Propofol, a widely used anaesthetic, confers antioxidative stress capability in the same process. But the connection between EMVs, H/R, and caveolae remains largely unclear...
2017: Oxidative Medicine and Cellular Longevity
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