Cell differentiation, vitamin

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

A most important function of vitamin A is in the control of cell differentiation and mrnover. PsA-trans-retinoic acid and 9-cw-retinoic acid (Figure 45-1) regulate growth, development, and tissue differentiation they have different actions in different tissues. Like the steroid hormones and vitamin D, retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes. There are two families of nuclear retinoid receptors the retinoic acid receptors (RARs) bind all-rrijw-retinoic acid or 9-c -retinoic acid, and the retinoid X receptors (RXRs) bind 9-cw-retinoic acid. 

Sokoloski, J.A., Hodnick, W.F., Mayne, S.T., Cinquina, C., Kim, C.S., and Sartorelli, A.C. 1997. Induction of the differentiation of HL-60 promyelocytic leukemia cells by vitamin E and other antioxidants in combination with low levels of vitamin D3 Possible relationship to NF-kappaB. Leukemia 11 1546-1553. 

Differentiation can be defined as the process of specialisation in terms of shape and function. An example is cell differentiation in plants, animals and humans a young cell, which is initially multifunctional, gradually acquires one specific function and shape. Specialisation is a refinement that is expressed in terms of shape, scent and colour. For example, fruits ripen, leaves change colour in the autumn, the growth of a shoot ends in a terminal bud and seeds become dormant. The primary components are converted into secondary components such as phenols, vitamins, aromas, wax, and so on. Thus differentiation in this context has a broader meaning than only the formation of a new plant organ . 

Vitamin D3 is transported to liver where it undergoes a hydroxylation at C-25 into 1a,25-dihydroxyvitamin D3 (calcitriol) (Fig. 64). In the kidney, it undergoes further hydroxylations at different sites, depending on the serum Ca + concentration. The most biologically active metabolite of vitamin D3 is calcitriol, which plays important roles in the regulation of calcium and phosphorus metabolism. It is used for treating bone diseases, but is also involved in the cell proliferation and the inducement of cell differentiation [151]. 

Altered vitamin A homeostasis, primarily manifested as decreased hepatic storage of vitamin A, is another established effect of PBBs in animals. Vitamin A is essential for normal growth and cell differentiation, particularly differentiation of epithelial cells, and some PBB-induced epithelial lesions resemble those produced by vitamin A deficiency. Because it is the primary storage site for vitamin A, the liver has a major role in retinol metabolism. Esterification of dietary vitamin A, hydrolysis of stored vitamin A, mobilization and release into the blood of vitamin A bound to retinol-binding protein, and much of the synthesis of retinol-binding protein occurs in the liver. 

Tretinoin. Tretinoin (Vesanoid), also known as all-tnmf-retinoic acid, is derived from vitamin A (retinol).86 This drug is not cytotoxic, but it may help cells differentiate and replicate at a more normal rate. However, the exact way that this agent affects cell differentiation is not known. Tretinoin is used primarily to treat certain forms of leukemia.7... 

Because vitamin A regulates epithelial cell differentiation and proliferation, there has been considerable interest in the apparent ability of retinol and related compounds to interfere with carcinogenesis. Vitamin A deficiency in humans enhances susceptibility to carcinogenesis. 

Vitamin A (retinol) is essential for normal growth and cell differentiation, particularly for epithelial cells. 2,3,7,8-TCDD has been shown to decrease the storage of vitamin A in rodents. Decreased ability to store vitamin A (retinol) was found in rats and guinea pigs however, partial recovery of the retinol content by week 16 postexposure was reported only in rats. A single oral dose of 2,3,7,8-TCDD caused a 70% reduction in the liver storage of retinol in rats when measured 2 months postexposure (Thunberg et al. 

Fig. 4. Schematic representation of the vitamin D-inicro-endocrine system (stem cell differentiation) showing the localization of l,25(OH)2D3 receptors as well as cells which have been shown to synthesize l,25(OH)2D.,.

Vitamin A is an essential fat-soluble compound acquired from the diet. The parent form of vitamin A is all-iram-retinol. Vitamin A is needed to maintain normal vision, normal reproduction (including spermatogenesis, conception, and placenta formation), and normal cell differentiation (including bone remodeling, maintenance of differentiated epithelial linings and skin, em-... 

Obeid, L.M., Linardic, C.M., Karolak, L.A., and Hannun, Y.A., 1993, Programmed cell death induced by ceramide, Science 259 1769-1771 Okazaki, T., Bell, R.M., and Hannun, Y.A., 1989, Sphingomyelin turnover induced by vitamin D3 in HL-60 cells. Role in cell differentiation. J. Biol. Chem. 264 19076-19080 Okazaki, T., Bielawska, A., Bell, R.M., and Hannun, Y. A., 1990, Role of ceramide as a lipid mediator of la, 25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J. Biol. Chem. 265 15823-15831... 

James SY, Williams MA, Newland AC, and Colston KW (1999) Leukemia cell differentiation cellular and molecular interactions of retinoids and vitamin D. General Pharmacology 32, 143-54. 

A (retinol, vitamin A alcohol) Fat 5,000 lU Vision, cell differentiation... 

Calcipotriol and tacalcitol are analogues of cal-citriol, the most active natural form of vitamin D (p. 742). Used topically they appear to be about as effective as dithranol and corticosteroid. They inhibit cell proliferation and encourage cell differentiation. Although they have less effect on calcium metabolism than does calcitriol, excessive use (greater than 100 g/week) can raise the plasma calcium concentration. 

---