Kerstin Danker

Charité Universitätsmedizin Berlin | Charité · Institute of Biochemistry

Oral inflammatory diseases are highly prevalent in the worldwide population. Topical treatment of inflammation is challenging due to dilution effects of saliva and crevicular fluid. Thus, there is a great medical need to develop smart anti-inflammatory drug delivery systems for mucosa treatment. We compared two promising anti-inflammatory dendritic...

A synthetic route for adhesive core-multishell (CMS) nanocarriers for application to the oral mucosa was established using mussel-inspired catechol moieties. The three CMS nanocarriers with 8%, 13%, and 20% catechol functionalization were evaluated for loading capacity using Nile red, showing an overall loading of 1 wt%. The ability of Nile red loa...

Objectives Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal...

Background One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Furthermore, the likelihood of drug resistance is reduced. Distinct alterations in tumor metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy....

Background: One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Further, the likelihood of drug resistance is reduced. Distinct alterations in tumour metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Re...

Periodontitis is one of the most common oral diseases worldwide and is caused by a variety of interactions between oral bacteria and the host. Here, pathogens induce inflammatory host responses that cause the secretion of proinflammatory cytokines such as IL-1β, IL-6, and IL-8 by oral epithelial cells. In various systems, it has been shown that inf...

Background: Despite an improvement of prognosis in breast and colon cancer, the outcome of the metastatic disease is still severe. Microevolution of cancer cells often leads to drug resistance and tumor-recurrence. To target the driving forces of the tumor microevolution, we focused on synergistic drug combinations of selected compounds. The aim i...

Neuroinflammation is often associated with pathological changes in the function of the blood-brain barrier (BBB) caused by disassembly of tight and adherens junctions that under physiological conditions are important for the maintenance of the BBB integrity. Consequently, in inflammation the BBB becomes dysfunctional, facilitating leukocyte travers...

Purpose: Previous studies have identified alkyl-phospholipids as promising compounds for cancer therapy by targeting constituents of the cell membrane and different signaling pathways. We previously showed that the alkylphospholipid Inositol-C2-PAF inhibits the proliferation and migration of immortalized keratinocytes and the squamous carcinoma-de...

Background and objectives: In the oral cavity, the mucosal tissues may develop a number of different pathological conditions, such as inflammatory diseases (gingivitis, periodontitis) and autoimmune disorders (eg, oral lichen planus) that require therapy. The application of topical drugs is one common therapeutic approach. However, their efficacy...

On the basis of surface tension and surface visco-elasticity measurements performed using profile analysis tensiometry with single pendent drops the surface properties of the alkyl phospholipid Inositol-C2-PAF were determined. Because of the very low bulk concentrations of Inositol-C2-PAF used in the studies, the obtained adsorption data had to be...

The blood-brain barrier (BBB) provides a dynamic and complex interface consisting of endothelial cells, pericytes and astrocytes, which are embedded in a collagen and fibronectin-rich basement membrane. This complex structure restricts the diffusion of small hydrophilic solutes and macromolecules as well as the transmigration of leukocytes into the...

Natural living cell membrane phospholipids undergo rapid and continuous turnover that provides essential signalling pathways controlling cell survival. Derived from (lyso)phosphatidylcholine, alkylphopspholipids (APL) were synthesized as metabolically stable analogues 50 years ago. The nature of the chemical structure of APLs allows them to be inse...

Psoriasis, a TNFα-governed inflammatory disorder with prominent dysregulation of cutaneous vascular functions, has evolved into a model disorder for studying anti-inflammatory therapies. We present experimental in vitro and in vivo data on inositoylated platelet activating factor (Ino-C2-PAF), the lead compound of a class of synthetic glycosylated...

The blood-brain barrier is necessary to provide an optimal environment for cerebral function. It consists of endothelial cells that interact through interendothelial tight junctions and form a barrier with low permeability. Therefore, the infiltration of lymphocytes into the central nervous system is limited. Pathological conditions, such as chroni...

Synthetic alkylphospholipids (APLs), exhibit similarity to the platelet-activating factor (PAF). These compounds have anti-proliferative effects on tumour cells and can therefore be regarded as a new class of drugs. Unlike classic cytostatic agents, synthetic alkylphospholipids do not interfere with the DNA or the mitotic spindle apparatus. Instead...

In cutaneous inflammatory diseases, such as psoriasis, atopic dermatitis and allergic contact dermatitis, skin-infiltrating T lymphocytes and dendritic cells modulate keratinocyte function via the secretion of pro-inflammatory cytokines. Keratinocytes then produce mediators that recruit and activate immune cells and amplify the inflammatory respons...

New alkylphospholipids (APLs) that are structurally derived from the platelet-activating factor (PAF) are promising candidates for anticancer treatment. After incorporation into cell membranes, APLs are able to interfere with a wide variety of key enzymes implicated in cell growth, motility, invasion, and apoptosis. In addition to the prototype 1-O...

Apoptosis is modulated by extrinsic and intrinsic signaling pathways through the formation of the death receptor-mediated death-inducing signaling complex (DISC) and the mitochondrial-derived apoptosome, respectively. Ino-C2-PAF, a novel synthetic phospholipid shows impressive antiproliferative and apoptosis-inducing activity. Little is known about...

New alkyl-phospholipids that are structurally derived from platelet-activating factor are promising candidates for anticancer treatment. The mechanism of action of derivatives of the platelet-activating factor is distinctly different from that of known DNA- or tubulin-targeting anticancer agents because they are incorporated into cell membranes, wh...

Cell expansion and metastasis are considered hallmarks of tumour progression. Therefore, efforts have been made to develop novel anti-cancer drugs that inhibit both the proliferation and the motility of tumour cells. Synthetic alkylphospholipids, compounds with aliphatic side chains that are ether linked to a glycerol backbone, are structurally der...

Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23-mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice. MMP-2 deficiency as well as therapeutic or pro...

Resistance arteries are the site of the earliest manifestations of many cardiovascular and metabolic diseases. Flow (shear stress) is the main physiological stimulus for the endothelium through the activation of vasodilatory pathways generating flow-mediated dilation (FMD). The role of FMD in local blood flow control and angiogenesis is well establ...

Integrins play a key role in cellular motility; an essential process for embryonic development and tissue morphogenesis, and also for pathological processes such as tumor cell invasion and metastasis. Recently, we showed that the cytoplasmic tail of integrin alpha(1) regulates the formation of focal complexes, F-actin cytoskeleton reorganization, a...

Integrin alpha3beta1 is a receptor for the extracellular matrix component laminin 5. To elucidate possible signaling pathways induced by integrin alpha3beta1, we looked for proteins that interact with the cytoplasmic part of the alpha3A integrin subunit. We identified several multifunctional proteins by affinity chromatography and subsequent MALDI-...

The search for specific anticancer drugs that do not interfere with DNA synthesis or influence the cytoskeleton has led to the development of modified phospholipids with antiproliferative properties. These compounds cause remodeling of the structure and function of plasma membranes. Recently, we described novel compounds, the glycosidated phospholi...

Binding of integrins to proteins of the extracellular matrix (ECM) provides structural and signaling information for biological processes such as cell proliferation, migration, neurite outgrowth, and differentiation. Integrins represent a family of heterodimeric transmembrane cell surface receptors. Besides connecting the ECM with the cytoskeleton,...

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by me...

Two new analogues derived from the platelet activating factor (PAF), containing glucosamine instead of the acetyl group, were synthesized, and their effect on the human keratinocyte cell line HaCaT was evaluated with respect to cytotoxicity, proliferation, adhesion, and migration. Starting with (R)-1,2-isopropylideneglycerol (3), the glycosylation...

Apoptosis is modulated by extrinsic and intrinsic signaling pathways through the formation of the death receptor-mediated death-inducing signaling complex (DISC) and the mitochondrial-derived apoptosome, respectively. Ino-C2-PAF, a novel synthetic phospholipid shows impressive antiproliferative and apoptosis-inducing activity. Little is known about...

IntroductionStructures of Synthetic Glycosidated Phospholipid AnaloguesAntiproliferative Effect and Cytotoxicity of Glycosidated Phospholipid Analogues in Cell Culture SystemsEffect of Glycosidated Phospholipid Analogues on Cell Matrix AdhesionMechanisms of ActionOutlook and New DevelopmentsAcknowledgementsReferences

Sialylation of glycoconjugates is essential for mammalian cells. Sialic acid is synthesized in the cytosol from N-acetylmannosamine by several consecutive steps. Using N-propanoylmannosamine, a novel precursor of sialic acid, we are able to incorporate unnatural sialic acids with a prolonged N-acyl side chain (e.g., N-propanoylneuraminic acid) into...

Sialylation of glycoproteins and glycolipids plays an important role during development, regeneration and pathogenesis of several diseases. The physiological precursor of all sialic acids is N-acetyl- D-mannosamine. The N-acyl side chain of sialic acid can be modified by exposure of cells to synthetic N-acyl-modified D-mannosamines. In a new experi...

Integrin adhesion receptors have been implicated in bidirectional signal transduction. The dynamic regulation of integrin affinity and avidity as well as post-ligand effects involved in outside-in signaling depends on the interaction of integrins with cytoskeletal and signaling proteins. In this study, we attempted to identify cytoplasmic binding p...

PC12 cells interact with several growth factors (e. g. EGF, FGF, and NGF) via specific tyrosine receptor kinases, resulting in cell proliferation or neuronal differentiation. The small GTPase Ras is known to be involved in downstream signaling of these growth factor receptors. Furthermore, cell-matrix interactions mediated by integrins, as well as...

Integrins are heterodimeric adhesion receptors consisting of alpha- and beta -subunits capable of binding extracellular matrix molecules as well as other adhesion receptors on neighbouring cells. These interactions induce various signal transduction pathways in many cell types, leading to cytoskeletal reorganization, phosphorylation and induction o...

The biological half-life time of many glycoproteins is regulated via terminal sialic acids. In this study we determined the half-lives of two different cell adhesion molecules, CEACAM1 and the α1-integrin subunit, in PC12-cells before and after biochemical engineering the side chain of sialic acids by the use of N-propanoylmannosamine. Both are tra...

Integrins are heterodimeric transmembrane proteins that mediate substrate adhesion and migration but also the bidirectional transfer of information across the plasma membrane via their cytoplasmic domains. We addressed the question of whether the very short cytoplasmic tail of the alpha1 integrin subunit of alpha1beta1 integrin is required for alph...

UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (UDP-GlcNAc 2-epimerase) is the key enzyme in the de novo synthesis pathway of neuraminic acid, which is widely expressed as a terminal carbohydrate residue on glycoconjugates. UDP-GlcNAc 2-epimerase is a bifunctional enzyme and catalyzes the first two steps of neuraminic acid synthesis...

N-Acetylneuraminic acid is a main constituent of glycoproteins and gangliosides. In many membrane-bound receptors it is the target for external stimuli. The key enzyme for its biosynthesis is the bifunctional enzyme UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, catalysing the first two steps of the biosynthesis in the cytosol. Th...

The rat cell-cell adhesion molecule C-CAM, a member of the carcinoembryonic antigen family, was shown to be expressed in various isoforms, differing in the length of the cytoplasmic domain. The long isoform C-CAML inhibits the growth of different malignant cells. Several studies suggest that it is involved in the mechanism of signal transduction. S...

Neuraminic acids are widely expressed as terminal carbohydrates on glycoconjugates and are involved in a variety of biological functions. The key enzyme of N-acetylneuraminic acid synthesis is UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase, which catalyses the first two steps of neuraminic acid biosynthesis in the cytosol. In this s...

Addition of polysialic acid (PSA) to the neural cell adhesion molecule, NCAM, represents a unique posttranslational modification. Polysialylation of NCAM is developmentally regulated and associated with neural regeneration and plastic processes, as well as learning and memory. Two enzymes, the polysialyltransferases ST8SiaII and ST8SiaIV, are known...

C-CAM (rat cell CAM/human CD66a) is ubiquitous and multifunctional. It is involved in intercellular adhesion, signal transduction and cell growth inhibition. Structurally, it is related to the carcinoembryonic antigen. In the present study serum, bile and urine of rats with liver diseases were analyzed for the presence of cell CAM. After bile duct...

Binding of integrins to the extracellular matrix (ECM) activates various signal transduction pathways and regulates gene expression in many cell types. Integrin-dependent cytoplasmic protein/protein interactions are necessary for activation of those signal transduction cascades. In our studies we investigated a possible association of pp125FAK, an...

The V-region represents one of three alternatively spliced segments in Xenopus fibronectin. Here, we identify this V-region as binding epitope of the monoclonal antibody (MAb 6D9) that we generated against Xenopus plasma fibronectin. By the use of this antibody we obtained new results that change the present view of the fibronectin expression patte...

Heat shock causes partial disruption of the segmentation pattern during somitogenesis in Xenopus as well as in other vertebrates. However, Xenopus undergoes a different type of somite formation than that of most vertebrates: Somites are formed by rotation of cell blocks out of the paraxial mesoderm. We attempted to determine whether or not the segm...

Two related but clearly different cDNA clones corresponding to elongation factor 1 alpha (EF-1 alpha) mRNAs were isolated from a Xenopus laevis gastrula-stage library. Whereas the nucleotide sequences of these two cDNAs differ within the coding region at 49 out of 1386 positions (3.5%), the derived amino acid sequences are completely identical, the...