Molecular dissection of the membrane aggregation mechanisms induced by monomeric annexin A2.

Annexins are a multigene family of proteins involved in aggregation and fusion processes of biological membranes. One of its best-known members is annexin A2 (or p36), capable of binding to acidic phospholipids in a calcium-dependent manner, as occurs with other members of the same family. In its heterotetrameric form, especially with protein S100A10 (p11), annexin A2 has been involved as a determinant factor in innumerable biological processes like tumor development or anticoagulation.

Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs.

Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression.

Structural and lipid-binding characterization of human annexin A13a reveals strong differences with its long A13b isoform.

Annexin A13 is the founder member of the vertebrate family of annexins, which are comprised of a tetrad of unique conserved domains responsible for calcium-dependent binding to membranes. Its expression is restricted to epithelial intestinal and kidney cells. Alternative splicing in the N-terminal region generates two isoforms, A13a and A13b, differing in a deletion of 41 residues in the former.

4F2hc-silencing impairs tumorigenicity of HeLa cells via modulation of galectin-3 and β-catenin signaling, and MMP-2 expression.

4F2hc is a type-II glycoprotein whose covalent-bound association with one of several described light chains yields a heterodimer mainly involved in large neutral amino acid transport. Likewise, it is well known that the heavy chain interacts with β-integrins mediating integrin-dependent events such as survival, proliferation, migration and even transformation. 4F2hc is a ubiquitous protein whose overexpression has been related to tumor development and progression.

Annexin-phospholipid interactions. Functional implications.

Annexins constitute an evolutionary conserved multigene protein superfamily characterized by their ability to interact with biological membranes in a calcium dependent manner. They are expressed by all living organisms with the exception of certain unicellular organisms. The vertebrate annexin core is composed of four (eight in annexin A6) homologous domains of around 70 amino acids, with the overall shape of a slightly bent ring surrounding a central hydrophilic pore.

Bile acids in the colon, from healthy to cytotoxic molecules.

Bile acids are natural detergents mainly involved in facilitating the absorption of dietary fat in the intestine. In addition to this absorptive function, bile acids are also essential in the maintenance of the intestinal epithelium homeostasis. To accomplish this regulatory function, bile acids may induce programmed cell death fostering the renewal of the epithelium.

Resistance to butyrate impairs bile acid-induced apoptosis in human colon adenocarcinoma cells via up-regulation of Bcl-2 and inactivation of Bax.

A critical risk factor in colorectal carcinogenesis and tumor therapy is the resistance to the apoptotic effects of different compounds from the intestinal lumen, among them butyrate (main regulator of colonic epithelium homeostasis). Insensitivity to butyrate-induced apoptosis yields resistance to other agents, as bile acids or chemotherapy drugs, allowing the selective growth of malignant cell subpopulations. Here we analyze bile acid-induced apoptosis in a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.

Histone deacetylase inhibitors upregulate MMP11 gene expression through Sp1/Smad complexes in human colon adenocarcinoma cells.

MMP-11 (stromelysin-3) is a matrix metalloproteinase associated with tumor progression and poor prognosis. Its expression was initially described exclusively in stromal cells surrounding tumors, but more recently it has also been detected in macrophages and hepatocarcinoma cells. Here we show MMP-11 expression in human epithelial colon adenocarcinoma cell lines (Caco-2, HT-29 and BCS-TC2).

Structural characterization and unfolding mechanism of human 4F2hc ectodomain.

4F2hc (CD98hc) is a multifunctional type II membrane glycoprotein involved in several functions as amino acid transport, cell fusion, β1-integrin-signaling and transformation. 4F2hc ectodomain has been crystallized and its three-dimensional structure determined. We have carried out a spectroscopical/structural characterization of the recombinant ectodomain in order to obtain information on its dynamic structure in solution and on its ability to form homodimers by itself in the absence of the transmembrane helix and of the potential interactions with the plasma membrane.

Biocompatibility and calcification of bovine pericardium employed for the construction of cardiac bioprostheses treated with different chemical crosslink methods.

The use of biological materials in the construction of bioprostheses requires the application of different chemical procedures to improve the durability of the material without producing any undesirable effects. A number of crosslinking methods have been tested in biological tissues composed mainly of collagen. The aim of this study was to evaluate the in vitro biocompatibility, the mechanical properties, and in vivo calcification of chemically modified bovine pericardium using glutaraldehyde acetals (GAAs) in comparison with glutaraldehyde (GA) treatment.

[Paediatric myofibroblastic tumours. A presentation of three cases].

There cases of paediatric inflammatory myofibroblastic tumours in different locations are presented. This a rare benign disease, that can develop into malignant forms. Clinical features are associated with the location.

Key role of the N-terminus of chicken annexin A5 in vesicle aggregation.

Annexins are calcium-dependent phospholipid-binding proteins involved in calcium signaling and intracellular membrane trafficking among other functions. Vesicle aggregation is a crucial event to make possible the membrane remodeling but this process is energetically unfavorable, and phospholipid membranes do not aggregate and fuse spontaneously. This issue can be circumvented by the presence of different agents such as divalent cations and/or proteins, among them some annexins.

Upregulation of annexin A1 expression by butyrate in human colon adenocarcinoma cells: role of p53, NF-Y, and p38 mitogen-activated protein kinase.

Annexin A1 is a member of a phospholipid and calcium binding family of proteins; it is involved in anti-inflammation and in the regulation of differentiation, proliferation, and apoptosis. Here, we show the existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level. Posttranscriptional mechanisms may also play an important role in maintaining constitutive annexin A1 expression.

Kinetic analysis of butyrate transport in human colon adenocarcinoma cells reveals two different carrier-mediated mechanisms.

Butyrate has antitumorigenic effects on colon cancer cells, inhibits cell growth and promotes differentiation and apoptosis. These effects depend on its intracellular concentration, which is regulated by its transport. We have analysed butyrate uptake kinetics in human colon adenocarcinoma cells sensitive to the apoptotic effects of butyrate (BCS-TC2, Caco-2 and HT-29), in butyrate-resistant cells (BCS-TC2.

The structure of human 4F2hc ectodomain provides a model for homodimerization and electrostatic interaction with plasma membrane.

4F2hc (CD98hc) is a multifunctional type II membrane glycoprotein involved in amino acid transport and cell fusion, adhesion, and transformation. The structure of the ectodomain of human 4F2hc has been solved using monoclinic (Protein Data Bank code 2DH2) and orthorhombic (Protein Data Bank code 2DH3) crystal forms at 2.1 and 2.

The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells.

The implication of the tetraspanin CD9 in cancer has received much recent attention and an inverse correlation between CD9 expression and the metastatic potential and cancer survival rate has been established for different tumor types. In contrast to the well-established role of CD9 in metastasis, very little is known about the involvement of this tetraspanin in the process of development of primary tumors. In the present study, we present evidence on the implication of CD9 in colon carcinoma tumorigenesis.

Acquisition of resistance to butyrate induces resistance to luminal components and other types of stress in human colon adenocarcinoma cells.

Butyrate, naturally produced by anaerobic fermentation of diet-fiber, is the major nutrient of colonocytes and also an important regulator of colonic epithelium renewal and physiology. Other luminal components, such as bile acids or bacterial products, influence these processes. The model system we used to analyze the influence of several luminal stressors is composed of a previously established cell line resistant to the apoptotic effects of butyrate and their parental butyrate-sensitive cells.

In vitro models for the study of the effect of butyrate on human colon adenocarcinoma cells.

The effect of butyrate has been analyzed on human colon adenocarcinoma cell lines with different properties regarding tumorigenicity, differentiation and resistance to apoptosis induced by this agent. Butyrate reduces cell proliferation, induces differentiation (according to alkaline phosphatase activity) and apoptosis, being these effects time- and concentration-dependent. The susceptibility to the cytotoxic effects of butyrate depends on the cell line considered and it is not directly related to tumorigenicity or differentiation.

Vitreous SiO2-CaO coatings on Ti6Al4V alloys: reactivity in simulated body fluid versus osteoblast cell culture.

Vitreous coatings of the SiO(2)-CaO system have been prepared on Ti6Al4V substrates by the sol-gel method. The textural parameters (porosity and roughness) and thickness of the films obtained increase when the concentration of the precursor solutions is raised. In vitro studies of these coatings have been performed using two approaches: soaking in simulated body fluid, and by growing osteoblasts on these materials.

Biochemical and mechanical behavior of ostrich pericardium as a new biomaterial.

We have performed a comparative analysis of glutaraldehyde-preserved ostrich pericardium, as a novel biomaterial, with bovine pericardium. The biochemical characteristics (histology, water content, amino acid composition, and collagen and elastin contents), mechanical properties, and in vivo calcification in a subcutaneous rat model were examined. Ostrich pericardium is slightly thinner and shows a higher water content (70+/-2% vs.

Effect of bile acids on butyrate-sensitive and -resistant human colon adenocarcinoma cells.

A controlled balance among cell proliferation, differentiation, and apoptosis is required for the maintenance of gastrointestinal mucosa; these processes are influenced by luminal components, such as butyrate and bile acids. Using butyrate-sensitive (BCS-TC2) and butyrate-resistant (BCS-TC2.BR2) human colon carcinoma cells, we wanted to establish whether colon carcinoma cells that acquire resistance to butyrate-induced apoptosis are also resistant to the cytotoxic effect of certain bile acids, contributing, in this way, to the progression of colon carcinogenesis.

Structure-function relationship in annexin A13, the founder member of the vertebrate family of annexins.

Annexin A13 is considered the original progenitor of the 11 other members of vertebrate annexins, a superfamily of calcium/phospholipid-binding proteins. It is highly tissue-specific, being expressed only in intestinal and kidney epithelial cells. Alternative splicing generates two isoforms, both of which bind to rafts.

Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5.

Butyrate induces differentiation and alters cell proliferation in intestinal-epithelial cells by modulation of the expression of several genes. Annexins are a superfamily of ubiquitous proteins characterized by their calcium-dependent ability to bind to biological membranes; their involvement in several physiological processes, such as membrane trafficking, calcium signaling, cell motility, proliferation, and differentiation has been proposed. Thus, we have analyzed changes in annexin A1 (AnxA1), annexin A2 (AnxA2), and annexin A5 (AnxA5) levels and localization in human colon adenocarcinoma cells differentiated by butyrate treatment or by culture in glucose-free inosine-containing medium.

Calcification and identification of metalloproteinases in bovine pericardium after subcutaneous implantation in rats.

The purpose of this study was to evaluate the influence of two anticalcification pre-treatments (chloroform/methanol and ethanol) and serum conditioning of glutaraldehyde-crosslinked bovine pericardium on the calcification degree and the presence of gelatinase activities in a subcutaneous implantation model in rats. Regarding calcification of the implants, glutaraldehyde control treatments showed a significatively higher calcification degree than pericardium treated with anticalcification reagents. Serum conditioning of glutaraldehyde treated tissues did not influence the calcification degree; moreover, no differences were found in these samples with the time of implantation (30 and 90 days).