Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Patent
1995-12-14
1998-11-10
Hendricks, Keith D.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
435 691, 4352523, 43525233, 4353201, 536 232, 536 235, 935 14, 935 29, 935 32, 935 70, 935 73, C12N 964, C12N 1557, C12N 1570, C12N 1585
Patent
active
058342907
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a recombinant polypeptide and to a nucleotide sequence encoding the polypeptide, to an expression system capable of expressing the polypeptide as well as to pharmaceutical and cosmetic compositions comprising the polypeptide and to the use of the polypeptide for various cosmetic or therapeutic purposes.
BRIEF DESCRIPTION OF THE INVENTION
The skin as an organ is of interest from biological, medical, and cosmetological points of view. There are a large number of skin diseases that are either organ-specific, e.g. psoriasis and eczemas, or are manifestations of general disease, such as general allergic reactions. The fact that there are skin-specific diseases can be considered as a proof of the existence of molecular mechanisms that are unique for the skin. Analogously, studies on skin-specific molecular processes are of importance for the understanding and treatment of skin disorders. It seems reasonable to assume that several of these processes in one way or another are related to the most specialized function of the skin, that is the formation of a physico-chemical barrier between body exterior and interior. The physico-chemical skin barrier is localized in the outermost layer of the skin, the stratum corneum.
The stratum corneum is the most specialized structure of the skin. It is the end product of the differentiation process of the epidermis, that is the stratified squamous epithelium which accounts for the outermost portion of the skin. The majority of the cells of the epidermis consist of keratinocytes in various states of differentiation. The lowermost keratinocytes, the basal cells, reside on a basal membrane in contact with the dermis, that is the connective tissue of the skin, and are the only keratinocytes that have dividing capability. A fraction of the basal cells continuously leaves the basal membrane and goes through a differentiation process which eventually makes the cells become building blocks of the stratum corneum. In this process the keratinocytes go through a number of adaptive changes. There is an increased content of cytoskeleton consisting of epidermis-specific cytokeratins. The intermediate filaments of contiguous cells are joined to a functional unit by an increased number of desmosomes. The most dramatic changes take place during the transition from the uppermost living cell layer, the stratum granulosum, to the non-viable stratum corneum in a process usually called keratinization. Covalently cross-linked proteins are deposited close to the inner aspect of the plasma membrane, forming a very resistant cell envelope. Furthermore a lipid-rich substance, originating in a keratinocyte-specific cell organel, is secreted to the extracellular space and, by forming lipid lamellae which surround the cells of the stratum corneum, constitutes the permeability barrier to hydrophilic substances. Finally all intracellular structures except the densely packed cytokeratin filaments disappear.
The cells of the stratum corneum, the corneocytes, are thus non-viable. This means that the regulation of various processes in the stratum corneum must be the result of a "programming" at a state where the keratinocytes are still viable. The turnover of the epidermis, which normally proceeds in about four weeks during which the cells are part of the stratum corneum for about two weeks, is ended by means of cell shedding from the skin surface in the process of desquamation. This process is an example of "programming" of the stratum corneum. A prerequisite for the function of the stratum corneum as a physico-chemical barrier is that its individual cells are held together by mechanically resistant structures, that is desmosomes. The degradation of desmosomes, which is a prerequisite for desquamation, must be regulated so as to give a cell shedding from the skin surface which balances de novo production of the stratum corneum without interfering with the barrier functions of the tissue.
Under a large number of pathological conditions in the skin of varying severity, there are
REFERENCES:
patent: 4652639 (1987-03-01), Stabinsky
Egelrud et al. "A chymotrypsin-like proteinase that may be involved in desquamation in plantar stratum corneum," Archiv. Dermatol. Res. 283:108-112, 1991.
Lundstrom et al. "Stratum corneum chymotryptic enzyme . . . ", Act Derm. Venereol. (Stockh) 71:471-474, 1991.
Egelrud et al. "The dependence of detergent-induced cell dissociation in non-palmo-plantar stratum corneum on endogenous proteolysis," Soc. Invest. Dermatol. 95:456-459, 1990.
Lundstrom et al. "Cell shedding from human plantar skin in vitro: Evidence of its dependence on endogenous proteolysis" Soc. Invest. Dermatol. 91:340-343, 1988.
Lundstrom et al. "Cell shedding from human plantar skin in vitro . . . ", Dermatol. Res. 282:234-237, 1990.
Lundstrom et al. "Evidence that cell shedding from plantar stratum corneum in vitro involves endogenous proteolysis," Soc. Invest. Dermatol. 94:216-220, 1990.
Lin et al (1989), -geneseq 25 database, Seq 10 p. 95121 (from EP 297913 A).
Hannson et al (1994) J Biol Chem 269:19420-426. "Cloning, Expression and Characterization of Stratum Corneum Chymotyptic Enzyme: A Skin-Specific Human Serine Proteinase".
Egelrud Torbjorn
Hansson Lennart
Astra Aktiebolag
Hendricks Keith D.
Moore William W.
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