Cellular differentiation, promotion

Decitabine (5-aza-deoxycytosine) is an analog of the nucleoside 2 -deoxycytidine. It is believed to exert its antineoplastic effects after phosphorylation and direct incorporation into DNA and by inhibition of the enzyme DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation or apoptosis. DNA hypomethylation is achieved at concentrations below those required to significantly inhibit DNA synthesis, which may promote restoration of function to genes associated with control of cellular differentiation and proliferation. Cytotoxicity in rapidly dividing cells may also result from covalent adducts between DNA methyltransferase and decitabine. 

Vitamin A (retinol) and retinoic acid are carotenoid oxidation compounds that are very important for human health. The main functions of retinoids relate to vision and cellular differentiation. With the exception of retinoids, it was only about 10 years ago that other carotenoid oxidation products were first thought to possibly exert biological effects in humans and were implicated in the prevention - or promotion of degenerative diseases. A review on this subject was recently published. ... 

A closely related challenge is the design of materials that interact with cells or living tissues to promote desired biological responses. Such responses might be cell attachment, cellular differentiation and organization into functional tissue, or promotion of in-growth of bone into an artificial prosthesis such as an artificial hip. 

Involved in the control of cellular growth is c-fos, whose expression is transiently activated by certain growth factors and tumour promoters and may also be activated during cellular differentiation and by cAMP. In neutrophils, c-fos mRNA is expressed at low rates, but transcripts are greatly increased by fMet-Leu-Phe (2-50 nM). This expression is transient (peak-... 

The cellular functions of protein tyrosine phosphatases are closely associated with signal transduction via protein tyrosine kinases. The growth and differentiation promoting signals mediated by protein tyrosine kinases include autophosphorylations and phosphorylation of effector proteins (see 8.1.4). According to current ideas, the activity of protein tyrosine phosphatases may have a negative or positive influence on signal transduction via protein tyrosine kinases. On the one hand, protein tyrosine... 

The mechanism of vanadium interaction with growth and differentiation pathways has been extensively studied [70], In tissue culture systems, vanadium has been shown to inhibit growth and, in some cases, modify DNA synthesis to block the G2-to-M transition. Cells blocked at M phase are susceptible to apoptosis, which can be stimulated by vanadium compounds. Vanadium compounds have also been shown to have mitotic effects stimulating growth, cell proliferation, or cell transformation. In some cases, vanadium compounds were able to promote cellular differentiation. Clearly, the addition of vanadium compounds would not have all of these... 

Ornithine decarboxylase (ODC) is the first enzyme in the polyamine biosynthesis pathway. Polyamines play essential roles in cell proliferation and differentiation and participate in macromolecular synthesis. Inhibitors of ODC block aspects of tumor promotion and induce cellular differentiation in several animal carcinogenesis models. Thus induction of ODC has been implicated as being important to carcinogenesis, and ODC activity is an intermediate biomarker of cell proliferation in studies... 

Notably, the effect of exogenous supply of ferrioxamine in Streptomyces is diverse it promotes growth in some strains, while it does not affect growth but stimulates cellular differentiation and/or secondary metabolism in... 

Retinoic acid, an endogenous retinoid, is an oxidized metabolite of retinol (vitamin A), and the most potent known inducer of differentiation in vitro (17-191. It is, therefore, most likely the form of vitamin A which promotes normal cellular differentiation. Because cancer is fundamentally a loss of cellular differentiation, physiological concentrations of retinoic acid may play an important role in the etiology of cancer. 

FA regulation of cellular differentiation and apoptosis has been reviewed (Rudolph et al., 2001). In general, differentiation was promoted by PUFAs such as AA, EPA, and DHA and metabolites such as PGE1 PGE2, and LTD4. The effect of PUFA on apoptosis was less clear-cut, with AA and GLA increasing apoptosis, whereas effects of EPA, DHA, and eicosanoids varied from stimulation to inhibition (Rudolph et al., 2001). 

Diacylglycerol is another product of the phosphodiesteratic cleavage of the Inosltides that has recently acquired enhanced importance. 1,2-Diacylglycerol activates a phospholipid- and Ca2+-dependent protein kinase C which is implicated in transmembrane signalling, tumor promotion and cellular differentiation.95,96 1,2-Diacyl-... 

Promotion of cellular differentiation is a promising postulated mechanism for chemoprevention. Several compounds have been reported to induce cell differentiation, including retinoids, vitamin D3, and genistein. " Resveratrol is capable of inducting differentiation in some hematological malignant cell lines, colon cancers, and neuroblastoma. Jang et al. reported that incubation of the promyelocytic leukemia HL-60 cells with resveratrol induces cell differentiation and reduction of DNA synthesis. 

In its second role, in the regulation of cellular differentiation, vitamin A is involved in the formation and protection of epithelial tissues and mucous membranes. In this way it has particular importance in growth, reproduction and immune response. Vitamin A is important in the resistance to disease and promotion of healing through its effect on the immune system and epithelial integrity. In addition, it acts, along with vitamins E and C and 3-carotene, as a scavenger of free radicals (see Box 5.2, p. 83). 

Both firefly luciferase (see below) and bacterial luciferase are sensitive reporters of gene expression suitable for the study of regulatory sequences (promoter, enhancer, and terminator) of cellular differentiation and morphogenesis, and of responses to environmental and developmental changes (53,54). The two reporter systems have been used in bacteria, yeast, fungi, insects, plants, and mammalian cells. As far as in vitro assays are concerned, both reporter systems may be considered equally useful. For in vivo applications, however, one system may turn out to be more suitable than the other due to the strengths and weaknesses inherent to each reporter system. 

The spatial and steric requirements for high affinity binding to protein kinase C (PKC), a macromolecule that has not yet been crystallized, were determined. Protein kinase C plays a critical role in cellular signal transduction and is in part responsible for cell differentiation. PKC was identified as the macromolecular target for the potent tumor-promoting phorbol esters (25). The natural agonists for PKC are diacylglycerols (DAG) (26). The arrows denote possible sites of interaction. 

MAP kinase signaling promotes differentiation ofPC12 cells. Adaptor proteins are able to regulate the time course of signaling events, and therefore the cellular outcome. 

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