Activation, mediators

Fluoride stimulates bone formation by protein kinase activation mediated effects on osteoblasts. Fluorides have been used in the treatment of osteoporosis, but their anti-fracture effect is not undisputed. 

Keaveney M, Struhl K Activator-mediated recruitment of the RNA polymerase machinery is the predominant mechanism for transcriptional activation in yeast. Mol Cell 1998 1 917. Lemon B, Tjian R Orchestrated response a symphony of transcription factors for gene control. Genes Dev 2000 l4 255l. Maniatis T, Reed R An extensive network of coupling among gene expression machines. Nature 2002 416 499. 

Lyden PD, Zivin JA, Clark WA, Madden K, Sasse KC, Mazzarella VA, Terry RD, Press GA. Tissue plasminogen activator-mediated thrombolysis of cerebral emboli and its effect on hemorrhagic infarction in rabbits. Neurology. 1989 39 703-708. 

It is clear from the preceding comments that there is no absolute distinction between the oxygenase activities mediated by dioxygenases. This is even less clear for heteroarenes than it is for carbocyclic compounds. An illustrative example is provided by Pseudomonas putida strain 86 in which 8-hydroxy-quinol-2-one is produced from quinol-2-one (Rosche et al. 1997). 

Creatinine phosphate (CP + ADP —> creatinine + ATP) AMP Dissolved 02 Inorganic pyrophosphate Energy reservoir for muscle activity Mediator of hormone activity Measurement of water quality Medical Starting material for several biological compounds... 

It appears that TNF-R55 is capable of mediating most TNF activities, whereas the biological activities induced via the TNF-R75 receptor are more limited. For example, TNF s cytotoxic activity, as well as its ability to induce synthesis of various cytokines and prostaglandins, is all mediated mainly/exclusively by TNF-R55. TNF-R75 appears to play a more prominent role in the induction of synthesis of T-lymphocytes. All of the biological activities mediated by TNF-R75 can also be triggered via TNF-R55, and usually at much lower densities of receptors. TNF-R75 thus appears to play more of an accessory role, mainly to enhance effects mediated via TNF-R55. 

These findings complete the panorama relative to the mechanisms of hormonal action mediated by nuclear receptors. Thus, gene activation mediated by nuclear receptors can respond to three clearly differentiated modalities (1) receptor bound to hormone and not phosphorylated, (2) receptor bound to hormone and phosphorylated, and (3) receptor not bound to hormone and phosphorylated (Filardo 2002 Lee et al. 2002 Powles 2002). 

Fig. 3. Synaptic localization of the mGluRs. The predominant localizations of the seven mGluR subtypes expressed in the CNS. The typical localizations of iGluRs and excitatory amino acid transporters (EAATs) are given, and the regulation of Glu release, iGluR signaling and ion channel activities mediated by the mGluRs is shown.

In summary, the scattered data available indicate that hemiester prodrugs generally undergo negligible hydrolysis at neutral pH in buffered solutions and in human plasma. In contrast, hydrolysis appears relatively fast in the presence of hepatic hydrolases. This would suggest limited first-pass metabolism and activation mediated mainly by liver hydrolases. 

While examples such as these provide evidence that strong interactions of negatively-charged membrane lipids with membrane proteins the role in maintaining asymmetric distributions of lipids aaoss biological membranes is unclear. In any event such effects are likely to be of minor importance relative to actively mediated phospholipid translocation processes. 

Hayashi Y (2000) The molecular genetics of recurring chromosome abnormalities in acute myeloid leukemia [In Process Citation]. Semin Hematol 37 368-380 Heery DM, Kalkhoven E, Hoare S, Parker MG (1997) A signature motif in transcriptional co-activators mediates binding to nuclear receptors [see comments]. Nature 387 733-736 Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y (1997) Adenoviral E 1 A-associated protein p300 is involved in acute myeloid leukemia with t(ll 22)(q23 ql3). Blood 90 4699-4704... 

UGTIAI has an important role in the metabolism of irinotecan, etoposide, epiru-bicine, and tipifamib. Irinotecan is a camptothecin derivative used in the treatment of metastatic colon cancer. Irinotecan is a prodrug since it is activated to Ethyl-10-hydroxycamptothecin (SN-38) by carboxyl esterase to exert its antitumor activity mediated by the inhibition of topoisomerase I. SN-38 undergoes UGTIAI-catalyzed glucuronide conjugation to form the inactive SN-38 glucuronide (SN-38G). 

Dichlorobenzidine is an effective inducer of its own metabolic activation (Iba 1987a). The enhancement of 3,3 -dichlorobenzidine mutagenesis has been associated with the induction of cytochrome P-450d (Iba and Thomas 1988), and may result in the elevation of its carcinogenicity. In other animal studies, 3,3 -dichlorobenzidine was also shown to be a potent inducer of hepatic microsomal enzymic activities mediated by cytochrome-P-448 and P-450 (Iba and Sikka 1983 Iba and Thomas 1988). Consequently, it has been suggested that the hepatocarcinogenicity of 3,3 -dichlorobenzidine may be due, at least in part, to the induction of hepatic cytochrome P-488 and DNA-adduction. 

Ozaki, Y, Qi, R., Satoh, K., Asazuma, N., and Yatomi, Y, Platelet activation mediated fiirough membrane glycoproteins Involvement of tyrosine kinases. Semin. Thromb. Haemost. 26, 47—51... 

Birnbaum, S.G., Gobeske, K.T., Auerbach, J., Taylor, J.R., and Arn-sten, A.F.T. (1999b) The role of alpha-l-adrenoceptor and PKC activation mediating stress-induced cognitive deficits. Soc Neu-rosci Abstr 25 608. 

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