Familial fibroblasts

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Interferons [alFN, piFN and ylFN]. Interferons are a family of glycosylated proteins and are cytokines which are produced a few hours after cells have been infected with a virus. Interferons protect cells from viral infections and have antiviral activities at very low concentrations ( 3 x 10 M, less than 50 molecules are apparently sufficient to protect a single cell). Double stranded RNA are very efficient inducers of IFNs. There are three main types of IFNs. The aIFNs are synthesised in lymphocytes and the piFNs are formed in infected fibroblasts. The a and P families are fairly similar consisting of ca 166 to 169 amino acids. Although ylFNs are also small glycosylated proteins (ca 146 amino acids), they are different because they are not synthesised after viral infections but are produced by lymphocytes when stimulated by mitogens (agents that induced cell division). 

Burgess WH, Maciag T (1989) The heparin-binding (fibroblast) growth-factor family of proteins. Annu Rev Biochem 58 575-606... 

Rather scanty evidence exists for the participation of free radicals in Alzheimer s disease and Down s syndrome. However, more recendy, reports have appeared that suggest possible free-radical involvement in the pathogenesis of these two conditions. Zemlan et al. (1989) repotted that the activity of the free-radical scavenging enzyme, SOD, was significantly increased in fibroblast cell lines derived from familial Alzheimer s and Down s patients. They hypothesized that the elevation in SOD activity observed in the Alzheimer patients supports the theory that paired helical filaments are formed by free-radical hydroxylation of proline residues. They further su ested that SOD levels might also be increased in the brains of Alzheimer s and Down s patients, and that the increase in SOD may reflect an enhanced generation of free radicals. 

The fibroblast growth factors comprise a gene family of nine members that share substantial sequence homology and have diverse effects in the nervous system 479... 

The isolation from a marine ascidian and subsequent structure determination of polycitone A (105) (Fig. 6) was first reported [52] by Kashman and coworkers in 1994. In this paper, the penta-O-methyl derivative was reported to inhibit the growth of SV40 transformed fibroblast cells at a concentration of 10 jtg/mL. Loya, Hizi and Kashman published [53] an extensive account of the biological activity of polycitone A in 1999 in which case inhibition of retroviral reverse transcriptases and cellular DNA polymerases was described. The isolation from an ascidian and structure determination of polycitone B (106) (Fig. 4) was subsequently reported [54] by Kashman and coworkers in 2000. Obviously, the presence of extensive bromination in both polycitone A and B make this family of compounds unique among the 3,4-diarylpyrrole natural products. 

Rosenthal, D.S., et al., Mechanisms of JP-8 jet fuel cell toxicity B. Induction of necrosis in skin fibroblasts and keratinocytes and modulation of levels of Bcl-2 family members, Toxicol. Appl. Pharmacol., 171, 107, 2001. 

Eukaryotic cells utilize an efficient transport system that delivers macromolecules fast and secure to their destination. In the case of the small GTP binding proteins of the Ras family the modified C-terminus seems to be sufficient for addressing the polypeptide to its target membrane (in the case of Ras itself the plasma membrane). Lipopeptides with the C-terminal structure of N-Ras (either a pen-tamer with a C-terminal carboxymethylation and farnesylation or a heptapeptide with a palmitoyl thioester in addition) and a N-terminal 7-nitrobenz-2-oxa-l,3-diazolyl (NBD) fluorophore were microin-jected into NIH3T3 fibroblast cells and the distribution of the fluorophore was monitored by confocal laser fluorescence microscopy. Enrichment of the protein in the plasma membrane was efficient only for peptides with two hydrophobic modification sites, while the farnesylated but not palmitoylated peptide was distributed in the cytosol.1121... 

Scallan, M.J., Raj, B.K.M., Calvo, B., Garin-Chesa, P., Sanz-Moncasi, M.P., Healey, J.H., Old, L.J. and Rettig, W.J. (1994) Molecular cloning of fibroblast activation protein alpha, a member of the serine protease family selectively expressed in stromal fibroblast of epithelial cancers. Proceedings of the National Academy of Sciences ofthe United States of America, 91, 5657-5661. 

In patients with familial hypercholesterolemia caused by defective LDL-receptor function, Lp(a) concentration in plasma is reported to be 2.5-3.0 times higher than in matched controls (HI 1, U8). In cultured fibroblasts of these patients, catabolism of Lp(a) and LDL is diminished as compared to controls. In fibroblasts of controls, the catabolism of Lp(a) is slower than that of LDL (F13, HI 1, Ml). 

Acidic and basic fibroblast growth factor family... 

Much less is known about the cytotoxic and antiproliferative effects of the 20(S)-PPT family of ginsenosides. Ginsenoside Rhi has been reported to inhibit proliferation of the NIH 3T3 mouse fibroblast cell line but did... 

Blander G, Guarente L (2004) The Sir2 family of protein deacetylases. Annu Rev of Biochem 73 417 35 Brinkmann H, Dahler AL, Popa C, Serewko MM, Parsons PG, Gabrielli BG, Burgess AJ, Saunders NA (2001) Histone hyperacetylation induced by histone deacetylase inhibitors is not sufficient to cause growth inhibition in human dermal fibroblasts. J Biol Chem 276 22491-22499... 

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