72 research outputs found
Claudin‐derived peptides are internalized via specific endocytosis pathways
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91364/1/j.1749-6632.2012.06567.x.pd
Mood Disorders Are Glial Disorders: Evidence from In Vivo Studies
It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Successful antidepressive treatment reduces S100B in major depression whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered. By indicating glial alterations without neuronal changes, serum S100B studies confirm specific glial pathology in mood disorders in vivo. S100B can be regarded as a potential diagnostic biomarker for mood disorders and as a biomarker for successful antidepressive treatment
Structure and function of claudins
AbstractClaudins are tetraspan transmembrane proteins of tight junctions. They determine the barrier properties of this type of cell–cell contact existing between the plasma membranes of two neighbouring cells, such as occurring in endothelia or epithelia. Claudins can completely tighten the paracellular cleft for solutes, and they can form paracellular ion pores. It is assumed that the extracellular loops specify these claudin functions. It is hypothesised that the larger first extracellular loop is critical for determining the paracellular tightness and the selective ion permeability. The shorter second extracellular loop may cause narrowing of the paracellular cleft and have a holding function between the opposing cell membranes. Sequence analysis of claudins has led to differentiation into two groups, designated as classic claudins (1–10, 14, 15, 17, 19) and non-classic claudins (11–13, 16, 18, 20–24), according to their degree of sequence similarity. This is also reflected in the derived sequence-structure function relationships for extracellular loops 1 and 2. The concepts evolved from these findings and first tentative molecular models for homophilic interactions may explain the different functional contribution of the two extracellular loops at tight junctions
A strategy for enrichment of claudins based on their affinity to Clostridium perfringens enterotoxin
<p>Abstract</p> <p>Background</p> <p>Claudins, a family of protein localized in tight junctions, are essential for the control of paracellular permeation in epithelia and endothelia. The interaction of several claudins with <it>Clostridium perfringens </it>enterotoxin (CPE) has been exploited for an affinity-based enrichment of CPE-binding claudins from lysates of normal rat cholangiocytes.</p> <p>Results</p> <p>Immunoblotting and mass spectrometry (MS) experiments demonstrate strong enrichment of the CPE-binding claudins -3, -4 and -7, indicating specific association with glutathione-S-transferase (GST)-CPE<sub>116–319 </sub>fusion protein. In parallel, the co-elution of (non-CPE-binding) claudin-1 and claudin-5 was observed. The complete set of co-enriched proteins was identified by MS after electrophoretic separation. Relative mass spectrometric protein quantification with stable isotope labeling with amino acids in cell culture (SILAC) made it possible to discriminate specific binding from non-specific association to GST and/or matrix material.</p> <p>Conclusion</p> <p>CPE<sub>116–319 </sub>provides an efficient tool for single step enrichment of different claudins from cell lysates. Numerous proteins were shown to be co-enriched with the CPE-binding claudins, but there are no indications (except for claudins -1 and -5) for an association with tight junctions.</p
Depletion of highly abundant proteins from human cerebrospinal fluid: a cautionary note
Visualization and Quantitative Analysis of Reconstituted Tight Junctions Using Localization Microscopy
Tight Junctions (TJ) regulate paracellular permeability of tissue barriers. Claudins (Cld) form the backbone of TJ-strands. Pore-forming claudins determine the permeability for ions, whereas that for solutes and macromolecules is assumed to be crucially restricted by the strand morphology (i.e., density, branching and continuity). To investigate determinants of the morphology of TJ-strands we established a novel approach using localization microscopy
On the Interaction of Clostridium perfringens Enterotoxin with Claudins
Clostridium perfringens causes one of the most common foodborne illnesses, which is largely mediated by the Clostridium perfringens enterotoxin (CPE). The toxin consists of two functional domains. The N-terminal region mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins. Claudin-3 and claudin-4 have been shown to be receptors for CPE with very high affinity. The toxin binds with weak affinity to claudin-1 and -2 but contribution of these weak binding claudins to CPE-mediated disease is questionable. cCPE is not cytotoxic, however, it is a potent modulator of tight junctions. This review describes recent progress in the molecular characterization of the cCPE-claudin interaction using mutagenesis, in vitro binding assays and permeation studies. The results promote the development of recombinant cCPE-proteins and CPE-based peptidomimetics to modulate tight junctions for improved drug delivery or to treat tumors overexpressing claudins
Trends in drug delivery through tissue barriers containing tight junctions
A limitation in the uptake of many drugs is the restricted permeation through tissue barriers. There are two general ways to cross barriers formed by cell layers: by transcytosis or by diffusion through the intercellular space. In the latter, tight junctions (TJs) play the decisive role in the regulation of the barrier permeability. Thus, transient modulation of TJs is a potent strategy to improve drug delivery. There have been extensive studies on surfactant-like absorption enhancers. One of the most effective enhancers found is sodium caprate. However, this modulates TJs in an unspecific fashion. A novel approach would be the specific modulation of TJ-associated marvel proteins and claudins, which are the main structural components of the TJs. Recent studies have identified synthetic peptidomimetics and RNA interference techniques to downregulate the expression of targeted TJ proteins. This review summarizes current progress and discusses the impact on TJs' barrier function
Heart protection and radical trapping by DMPO during reperfusion in isolated working rat hearts
Inverse relationship between ESR spin trapping of oxyradicals and degree of functional recovery during myocardial reperfusion in isolated working rat heart
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