الفهرس 
Chapter I: AquaporinsOnly 14 pages are availabe for public view
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Abstract
Water is the single most abundant substance in cells and organisms and is indispensable for life. The water content of an organism is related to its age and metabolic activity, being highest in embryo (90% -95%) and decreasing progressively in old age. Aquaporins are integral membrane proteins from a larger family of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. The plasma membranes of a variety of different animal and plant cells contain aquaporins through which water can flow more rapidly inside the cell than by diffusing through the phospholipid bilayer. Peter Agre in 2003 received the Nobel Prize in Chemistry for his discovery of the first aquaporin in 1992 with the research group led by him. The structure of AQPs is unique. AQPs comprise four subunits, each with a water-conducting pore.
Aquaporin proteins are made up of six transmembrane α-helices arranged in a right handed bundle, with the amino and the carboxyl termini located on the cytoplasmic surface of the membrane. The amino and carboxyl halves of the sequence show similarity to each other, in what appears to be a tandem repeat. Aquaporins form tetramers in the cell membrane, with each monomer acting as a water channel. The different aquaporins contain differences in their peptide sequence, which allows for the size of the pore in the protein to differ between aquaporins. The resultant size of the pore directly affects what molecules are able to pass through the pores. Thirteen mammalian aquaporins have been found, AQP0-12. The names represent each aquaporins respective order of discovery.The most common classification is to place AQP0, AQP1, AQP2, AQP4, AQP5, AQP6 and AQP8 as aquaporins and AQP3, AQP7, AQP9 and AQP10 as aquaglyceroporins can transport water to varying degrees, as well as small solutes, particularly glycerol. Phenotype studies of transgenic AQPs knockout mouse models, and cases of humans with AQPs mutations, have shown some essential roles for AQPs. These include a urinary concentrating function, exocrine glandular fluid secretion, vasogenic brain oedema formation, regulation of intracranial and intraocular pressure, fat metabolism, hyperinsulinemia, Sjogren’s syndrome, glaucoma, nephrogenic diabetes insipidus, lymph node metastatic carcinoma, tumor growth, tumour angiogenesis and cell migration.
Aquaporin-3, belongs to the aquaglyceroporin subtype of the AQP family. It acts as a membrane channel for water and other small solutes such as glycerol and urea, and plays a major role in fluid homeostasis. It is expressed in many epithelial cells, such as epidermal keratinocytes in rat, mouse and human skin. Aquaporin-3 is expressed in cells from the basal to the granular layers but disappears in the stratum corneum (SC). The skin, the body’s largest organ, is the outer covering of the body. It forms a barrier that helps prevent harmful microorganisms and chemicals from entering the body and it also prevents loss of life sustaining body fluids. It protects the vital structures inside the body from injury and from the potentially damaging ultraviolet rays of the sun. The skin also helps regulate body temperature, excretes some waste products, and is an important sensory organ. The basal and suprabasal living layers of the skin are composed of 75% water while the SC contains 10–15% water. Therefore, the water AQP3 channel may account for increased water impermeability at the stratum granulosum–statum corneum interface.
AQP1, 3, 5, 7, 9 and 10 may be expressed in human skin, but only AQPs of the epidermis, sweat glands and sebaceous glands are strictly related to skin physiology. In sweat glands AQP5 has been shown to be important for water secretion. In the epidermis, AQP1 was found in melanocytes. AQP3 is the most abundant aquaporin. It is expressed in cells from the basal to the granular layers but disappears in the stratum corneum (SC). and has been attributed a role in the transport and metabolism of glycerol. In addition, AQP3 play important role in skin hydration, keratinocyte proliferation and differentiation, wound healing, skin tumorigenesis and in skin immunity in human. AQP3-null mice have relatively dry skin, reduced skin elasticity, and delayed recovery of barrier function after removal of the (SC).
Altered AQP3 expression and its down regulation, is mostly result in dehydration, excessive proliferation of the skin and altered of the skin immunity result in a variety of skin diseases such as atopic eczema, erythema toxicum neonatorum, aquagenic wrinkling of the palms, psoriasis, vitiligo and nonmelanoma skin cancer. Also the detected correlation of expression percentage of AQP3 and the tumor grade may open a new avenue for the use of AQP3 expression as a prognostic marker in cutaneous SCC.
Adequate cutaneous hydration remains the key to ensuring efficacy for therapeutic and multiple cosmetic/personal care products. AQPs appear to be key protein targets to improve the resistance and quality of the skin surface as well as to improve aging and sun exposure- induced dryness. The green coffea arabica L. seed oil, hydrolyzed jojoba esters and retinoic acid increases aquaporin 3 expression in normal human Skin. AQPs target inhibitors and AQPs stimulators of their expression, even AQP gene transfer which still under study, are developed to provide new therapeutic strategy in anticancer treatment. However, there is still a long way to clearly elucidate the specificity of AQPs in the pathogenesis, metabolisms, and controls of various cancers, or resistance and tolerance to anticancer therapies. The process in AQPs target inhibitors development has also been slow and none AQP associated drugs has been applied for clinical anticancer therapy by far.