bromochloroacetic-acid and Disease

Intermediate filaments are major phosphoproteins. The complex patterns of intermediate filament phosphorylation make up a poorly understood code reflecting cytoskeletal properties and cellular function through an intense crosstalk with multiple signaling pathways. This review focuses on the epithelial keratin intermediate filaments highlighting the tight-knit relationship of keratin phosphorylation and network organization during cell division and apoptosis, and the importance of keratin phosphorylation during epithelial stress responses. The occurrence of keratin phosphorylation in genetic skin diseases and acquired diseases of simple epithelial tissues in liver, pancreas, and colon will be discussed. Finally, we will review the role of keratin phosphorylation in cancer with an emphasis on migration.

Topics: Animals; Cytoskeleton; Disease; Epithelial Cells; Humans; Keratins; Phosphorylation; Protein Binding

The cytoprotective keratins (K) compose the intermediate filaments of epithelial cells and their inherited and spontaneous mutations give rise to keratinopathies. For example, mutations in K1/K5/K10/K14 cause epidermal skin diseases whereas simple epithelial K8/K18/K19 variants predispose to development of several liver disorders. Due to their abundance, tissue- and context-specific expression, keratins constitute excellent diagnostic markers of both neoplastic and non-neoplastic diseases. During injury and in disease, keratin expression levels, cellular localization or posttranslational modifications are altered. Accumulating evidence suggests that these changes modulate multiple processes including cell migration, tumor growth/metastasis and development of infections. Therefore, our understanding of keratins is shifting from diagnostic markers to active disease modifiers.

Topics: Animals; Biomarkers; Disease; Epithelial Cells; Humans; Intermediate Filaments; Keratins; Mutation; Protein Processing, Post-Translational

The epidermis is a stratified epithelium that relies on its cytoskeleton and cell junctions to protect the body against mechanical injury, dehydration, and infections. Keratin intermediate filament proteins are involved in many of these functions by forming cell-specific cytoskeletal scaffolds crucial for the maintenance of cell and tissue integrity. In response to various stresses, the expression and organization of keratins are altered at transcriptional and posttranslational levels to restore tissue homeostasis. Failure to restore tissue homeostasis in the presence of keratin gene mutations results in acute and chronic skin disorders for which currently no rational therapies are available. Here, we review the recent progress on the role of keratins in cytoarchitecture, adhesion, signaling, and inflammation. By focusing on epidermal keratins, we illustrate the contribution of keratin isotypes to differentiated epithelial functions.

Topics: Animals; Disease; Epidermis; Humans; Keratins; Organ Specificity; Protein Binding; Protein Processing, Post-Translational

Topics: Animals; Disease; Epithelial Cells; Humans; Keratins; Phenotype

The cytoplasm of animal cells is structured by a scaffolding composed of actin microfilaments, microtubules, and intermediate filaments. Intermediate filaments, so named because their 10-nanometer diameter is intermediate between that of microfilaments (6 nanometers) and microtubules (23 nanometers), assemble into an anastomosed network within the cytoplasm. In combination with a recently identified class of cross-linking proteins that mediate interactions between intermediate filaments and the other cytoskeletal networks, evidence is reviewed here that intermediate filaments provide a flexible intracellular scaffolding whose function is to structure cytoplasm and to resist stresses externally applied to the cell. Mutations that weaken this structural framework increase the risk of cell rupture and cause a variety of human disorders.

Topics: Animals; Axons; Cytoplasm; Cytoskeletal Proteins; Disease; Genetic Diseases, Inborn; Humans; Intermediate Filament Proteins; Intermediate Filaments; Keratinocytes; Keratins; Microtubules; Mutation; Neurons

Topics: Animals; Cell Biology; Disease; Disease Models, Animal; Humans; Intermediate Filaments; Keratins

Topics: Alleles; Animals; Crohn Disease; Diabetes Mellitus, Type 2; Disease; DNA; Evolution, Molecular; Female; Genome, Human; Humans; Interleukin-18; Keratins; Liver Cirrhosis, Biliary; Male; Neanderthals; Optic Disk; Sequence Analysis, DNA; Smoking

Topics: Animals; Cell Cycle; Cells; Clinical Trials as Topic; Disease; Humans; Keratins; Mutation; Signal Transduction; Translational Research, Biomedical

Exponential advances in the quantitation of DNA variation and epigenetic states seem poised to convert much of biological research into a statistical exercise. But these developments also invite us to reimagine well-worn biological concepts on a grander scale. Somatic mosaicism refers to postzygotic mutations persisting in the individual, occasionally conspicuous to dermatologists as Blaschkoid, checkerboard, phylloid and patchy morphologies. A thoughtful examination of cutaneous mosaicism suggests, however, that virtually all of us may be somatic mosaics. Such genetic variability within individuals might explain localized presentations of disease and implies that some tissues literally evolve throughout life. We discuss here (i) the likely ubiquity of somatic mosaicism, (ii) the broad range of possible biological consequences and (iii) how experimentalists and clinicians may begin establishing genotype-to-phenotype correlates.

Topics: Cell Lineage; Clone Cells; Disease; Genetic Association Studies; Humans; Keratins; Mosaicism; Mutation; Neoplasms; Nevus; Sequence Analysis, DNA; Skin; Skin Diseases

The aim of the present paper was to analyse, on patient and implant basis, factors related to peri-implant lesions.. Two hundred and eighteen patients treated with titanium implants were examined for biological complications at existing implants 9-14 years after initial therapy. The effects of several potentially explanatory variables, both on patient and on implant levels, were analysed.. On the implant level, the presence of keratinized mucosa (p = 0.02) and plaque (p = 0.005) was associated with mucositis (probing depth > or =4 mm + bleeding on probing). The bone level at implants was associated with the presence of keratinized mucosa (p = 0.03) and the presence of pus (p < 0.001). On the patient level, smoking was associated with mucositis, bone level and peri-implantitis (p = 0.02, <0.001 and 0.002, respectively). Peri-implantitis was related to a previous history of periodontitis (p = 0.05).. Individuals with a history of periodontitis and individuals who smoke are more likely to develop peri-implant lesions.

Topics: Aged; Alveolar Bone Loss; Dental Implants; Dental Plaque; Disease; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Mouth Mucosa; Periodontal Diseases; Periodontal Pocket; Periodontitis; Risk Factors; Smoking; Suppuration; Titanium

Lichen amyloidosus (LA) is generally said to be a pruritic type of amyloidosis of unknown cause. Histopathologically, it is characterized by epidermal changes of lichen simplex chronicus and by deposits of amyloid in the papillary dermis that are derived from keratin peptides of necrotic keratinocytes. Chronic scratching is responsible for the development of lichen simplex chronicus and may lead to necrosis of individual keratinocytes.. Our purpose was to evaluate whether chronic scratching may also be responsible for the formation of amyloid in LA.. We studied patients with LA in regard to histopathologic findings, onset of pruritus, associated diseases, and response to treatment.. In most cases, pruritus had preceded the skin lesions. Eight of nine patients suffered from diseases other than LA that may be associated with pruritus. Histopathologically, amyloid was confined to areas that also showed signs of lichen simplex chronicus. Systemic treatment with sedating antihistamines and intense local treatment with corticosteroids were found to be effective.. LA is considered to be a variant of lichen simplex chronicus in which scratching leads to necrosis of keratinocytes and eventually to the formation of amyloid in the papillary dermis. Because chronic scratching seems to be the cause and not the result of the deposits of amyloid, treatment should be directed at the amelioration of pruritus.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Aged; Amyloid; Amyloidosis; Antipruritics; Chronic Disease; Collagen; Disease; Female; Histamine H1 Antagonists; Humans; Keratinocytes; Keratins; Keratosis; Leg Dermatoses; Male; Middle Aged; Necrosis; Neurodermatitis; Pruritus; Remission Induction; Skin; Skin Diseases

Topics: Disease; Epithelium; Female; Humans; Keratins; Keratosis, Actinic; Vagina; Vaginal Diseases; Vaginal Smears

Topics: Disease; Gingiva; Gingival Diseases; Humans; Keratins