Keratins characterization

Bartek J, Vojtesek B, Staskova Z, Bartkova J, Kerekes Z, Rejthar A, Kovarik J (1991) A series of 14 new monoclonal antibodies to keratins characterization and value in diagnostic histopa thology. J Pathol 164(3) 215 224... 

A number of skin diseases, mainly characterized by blistering, have been found to be due to mutations in genes encoding various keratins. Three of these disorders are epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic pahnoplantar kerato-derma. The blistering probably reflects a diminished capacity of various layers of the skin to resist mechanical stresses due to abnormalities in microfilament strucmre. 

In squamous cell carcinomas, focal expression of K1 and K10, usually in relation to maturation and keratinization, can be observed regardless of whether they are derived from the skin or from internal organs (for references, see Moll 1998). However, quantitatively, squamous cell carcinomas embark on an alternative maturation pathway characterized by abundant expression of K6 and K16. In summary, basal-type keratins K5 and K6 are useful as general markers for tumors derived from basal (K5/14+ progenitor) cells, whereas K1 and K10 can be regarded as keratinization markers and therefore as squamous differentiation markers. 

Squamous cell carcinomas of different sites of origin are generally characterized by a predominance of stratified-epithelial/keratinocyte-type keratins but may coexpress certain simple-epithelial keratins (for details, see Moll 1998). Most of these... 

In another approach, Parnigotto and coworkers reconstructed corneal structures in vitro by using corneal stroma containing keratocytes to which corneal epithelial cells from bovine primary cultures were overlaid [73], However, this particular corneal model did not contain an endothelial layer. This model was histochemically characterized and the toxicity of different surfactants was tested using MTT methods. This stroma-epithelium model has been reported to show a cornea-like morphology, where a multilayered epithelial barrier composed of basal cells (of a cuboidal shape) and superficial cells (of a flattened shape) is noted. Furthermore, the formation of a basement membrane equivalent and expression of the 64-kDa keratin were reported, indicating the presence of differentiated epithelial cells. The toxicity data for various surfactants obtained with this model correlate well with those seen by the Draize test [73], However, this corneal equivalent was not further validated or used as a model for permeation studies. 

It is an autoimmune disease which is characterized by marked increase in undifferentiated epidermal cell proliferation and can increase the number of superficial cells having abnormal keratinization. 

Common cold, influenza, recovery period of influenza, bronchitis, pneumonia, chronic rhinitis, tuberculosis and other infectious diseases caused by bacteria and viruses, diabetes, peptic ulcer, irritable bowel syndrome, constipation and hemorrhoids, skin diseases that are characterized by dryness of the skin lesions, such as disorders of keratinization and senile pruritus. 

The head domain in trichocyte (or hair) keratins has been characterized by Parry and North (1998) and Parry et al. (2002) and shown to consist of two domains—a basic one (NB) at the N-terminal end of the head domain (27 and 70 residues long, respectively, for Type I and Type II chains) and an acidic one (NA) lying between the rod and NB. The latter is 29 and 34 residues long for Type I and Type II chains, respectively. Importantly, however, NA is homologous to HI in the respective chain types of epidermal keratins. There can therefore be little, if any, doubt that the role of these regions in trichocyte and epidermal keratins is... 

The head and tail domains in keratin molecules generally contain a multitude of sites that allow keratin IFs to form covalent bonds with other proteins. For example, in the case of the keratin IFs in the inner root sheath, lysine to glutamine crosslinks have been characterized between the head and (more often) the tail domains in (generally) both Type I and Type II chains, envoplakin, epiplakin, the SPR2 (small proline-rich) family, and trichohyalin (Steinert et al., 2003). Likewise, in noninner root... 

Histologically, the disease is characterized by a loss of adhesion between suprabasal keratinocytes (acantholysis) and abnormal keratinisation (dyskeratosis) of the epidermis. In HHD, acantholysis is the most prominent histological feature while in the clinically related Darier disease (OMIM 124200), dyskeratosis is much more apparent. Ultrastructural analysis of acantholytic cells reveals perinuclear aggregates of keratin filaments that have retracted from desmosomes (Harada et al., 1994 Hashimoto et al., 1995 Metze et al., 1996). 

Stratum basale is a single layer composed of stem cells and their derivative cells. It is attached to the basement membrane by hemidesmo-somes.48 The cells in this layer are columnar or cuboidal in shape and characterized by large nuclei (high nuclear-cytoplasmic ratio) and keratin filaments (tonofilaments). The basal layer contains keratins K14 and K15, melanocytes (which are pigment-forming cells), Langerhans... 

The hair matrix possesses a large monitoring window (months/years) that allows a retrospective analysis and the study of past history. Hair is also characterized by a high stability and a minimum possibility of adulteration [41, 42], The structure of the hair can be considered as a repeated network of keratin fibers. There are also melanins, lipids, and all the compounds of cells that led to the formation of the stem. The growth of hair is in the range of 0.6-1.4 cm/month [43,44],... 

Dry, scaly skin is characterized by a decrease in the water retention capacity of the stratum corneum (SC),1 with water content diminished to less than 10%. Barrier function of the SC is usually declined, and transepidermal water loss (TEWL) is increased because of an abnormality on barrier homeostasis.2 People feel tightness of their skin, and the skin surface becomes rough, scaly, and sensitive. Hyperkeratosis, abnormal scaling, and epidermal hyperplasia are usually observed in the dry skin.2 Keratinization also shows abnormal features.2 These phenomena are commonly observed in atopic dermatitis and psoriasis.3 Dermatitis induced by environmental factors such as exposure to chemicals, low humidity, and UV radiation also shows these features. Thus, many researchers have been investigating the cause and treatment of dry skin, and there is currently great interest in adequate model systems for dry skin studies. In this chapter, I will describe several model systems of dry skin for clinical research of dermatitis associated with skin surface dryness and also mention recent studies to improve the dry skin. 

The four protein conformations that provide mechanical stability to cells, tissues, and organs include the random coil or amorphous structure that characterizes a part of the structure of elastin, the a helix, which is represented by the keratin molecule, the collagen triple helix, and the p structure of silk. In humans the P structure is found only in short sequences connecting parts of other structures such as the a helix, but serves as an example of the relationship between protein structure and properties. The ultimate tensile strength and modulus of each structure differs as discussed below. 

Keratin in the cortex comprises 85% or more of the mass of the hair shaft. Cortical keratin is composed of two types of structural proteins, matrix proteins and fibrous proteins. 2-1 Matrix proteins have a high sulfur content and contain polypeptides with a molecular weight of approximately 10 to 28 kDa. Fibrous proteins are embedded in matrix proteins and are characterized by a low sulfur content. They have a molecular weight of approximately 40 to 58 kDa. Also, matrix proteins have a nonhelical structure and are readily soluble at pH 4.5 in 0.5 M KCl, whereas fibrous proteins exhibit a helical structure and are insoluble in this same solution. 

The structure, organization, and ratio of matrix and fibrous proteins contribute to the physiochemical properties of keratinous tissues. For example, a primary difference between hair and nails is the arrangement of fibrous proteins and the concentration of matrix proteins present in each tissue. In cells destined to form the cortex of hair, fibrous proteins are oriented to form filaments which cluster to form fibrils. In the keratogenous zone, fibrils undergo lateral fusion to ultimately produce the cortex. The medulla also contains keratin which has been characterized as a collection of irregular fibrous proteins. Fibrous proteins form a trabecular framework comprising 95% of the medulla, and medullary proteins are less resistant to chemical degradation than proteins in the cortex. The cell membrane complex. 

Baden, H. R, Characterization of hair keratins, in Hair Research Status and Future Aspects, Orfanos, C. E., Montagna, W., and Stuttgen, G., Eds., Springer-Verlag, Berlin, 1981, 73. 

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