Desmin: molecular interactions and putative functions of the muscle intermediate filament protein

Desmin is the intermediate filament (IF) protein occurring exclusively in muscle and endothelial cells. There are other IF proteins in muscle such as nestin, peripherin, and vimentin, besides the ubiquitous lamins, but they are not unique to muscle. Desmin was purified in 1977, the desmin gene was characterized in 1989, and knock-out animals were generated in 1996. Several isoforms have been described. Desmin IFs are present throughout smooth, cardiac and skeletal muscle cells, but can be more concentrated in some particular structures, such as dense bodies, around the nuclei, around the Z-line or in costameres. Desmin is up-regulated in muscle-derived cellular adaptations, including conductive fibers in the heart, electric organs, some myopathies, and experimental treatments with drugs that induce muscle degeneration, like phorbol esters. Many molecules have been reported to associate with desmin, such as other IF proteins (including members of the membrane dystroglycan complex), nebulin, the actin and tubulin binding protein plectin, the molecular motor dynein, the gene regulatory protein MyoD, DNA, the chaperone alphaB-crystallin, and proteases such as calpain and caspase. Desmin has an important medical role, since it is used as a marker of tumors' origin. More recently, several myopathies have been described, with accumulation of desmin deposits. Yet, after almost 30 years since its identification, the function of desmin is still unclear. Suggested functions include myofibrillogenesis, mechanical support for the muscle, mitochondrial localization, gene expression regulation, and intracellular signaling. This review focuses on the biochemical interactions of desmin, with a discussion of its putative functions.

Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp) motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

An empirical comparison of atypical bulimia nervosa and binge eating disorder

The International Classification of Diseases, 10th edition (ICD-10) defines atypical bulimia nervosa (ABN) as an eating disorder that encompasses several different syndromes, including the DSM-IV binge eating disorder (BED). We investigated whether patients with BED can be differentiated clinically from patients with ABN who do not meet criteria for BED. Fifty-three obese patients were examined using the Structured Clinical Interview for DSM-IV and the ICD-10 criteria for eating disorders. All volunteers completed the Binge Eating Scale (BES), the Beck Depression Inventory, and the Symptom Checklist-90 (SCL-90). Individuals fulfilling criteria for both ABN and BED (N = 18), ABN without BED (N = 16), and obese controls (N = 19) were compared and contrasted. Patients with ABN and BED and patients with ABN without BED displayed similar levels of binge eating severity according to the BES (31.05 ± 7.7 and 30.05 ± 5.5, respectively), which were significantly higher than those found in the obese controls (18.32 ± 8.7; P < 0.001 and P < 0.001, respectively). When compared to patients with ABN and BED, patients with ABN without BED showed increased lifetime rates of agoraphobia (P = 0.02) and increased scores in the somatization (1.97 ± 0.85 vs 1.02 ± 0.68; P = 0.001), obsessive-compulsive (2.10 ± 1.03 vs 1.22 ± 0.88; P = 0.01), anxiety (1.70 ± 0.82 vs 1.02 ± 0.72; P = 0.02), anger (1.41 ± 1.03 vs 0.59 ± 0.54; P = 0.005) and psychoticism (1.49 ± 0.93 vs 0.75 ± 0.55; P = 0.01) dimensions of the SCL-90. The BED construct may represent a subgroup of ABN with less comorbities and associated symptoms.