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121.
Ivan A. ShibleyJr. Michael D. Gavigan Sam N. Pennington 《Alcoholism, clinical and experimental research》1995,19(1):209-215
An extraordinarily diverse literature describes the cellular/tissue systems in which the molecular effects of both acute and chronic alcohol exposure seem to be mediated by changes in polyamine levels and/or ornithine decarboxylase (ODC) activity. The single unifying factor that links most of these studies is that they all, in some way, involve tissues that are undergoing relatively rapid cell division. Non-dividing cells expressing the NMDA receptor are a notable exception in that ethanol and the polyamines seem to act via discrete regions of that receptor. Under most cellular conditions, ODC activity is a reflection of the relative tissue polyamine content, and an increase in ODC activity and polyamine content seems to be one of the early events in the progression of quiescent cells toward cell division. Thus, it is not surprising that ethanol, which has been widely reported to delay cell division, should be found to interact with the ODC/ polyamine pathway. Perhaps the most unique aspect of these studies is the fact that, with rare exception, both acute and chronic ethanol exposure have been found to slow growth and to lower tissue polyamine (putrescine) content. Furthermore, in most studies, the ethanol-induced suppression of cell division could be overcome by the administration of exogenous putrescine. These data suggest that the ethanol-induced suppression of cell division resulted from the loss of putrescine. In addition, because the cells were able to respond to the exogenous putrescine, the studies suggest that the signaling pathway remained intact beyond the polyamine synthesis step. Increased ODC activity (and polyamines?) has been reported during the perinatal and postnatal periods in fetal animals exposed to ethanol during early development. Although not examined in all models, the perinatal/postnatal increase in fetal ODC activity may be a compensatory response to an initial loss of ODC activity, as the organism attempted to overcome the alcohol-induced growth suppression. 相似文献
122.
Nashaat Turkman Juri G. Gelovani Mian M. Alauddin 《Journal of labelled compounds & radiopharmaceuticals》2011,54(1):33-37
Polyamines are naturally occurring polycations derived from amino acids via decarboxylation by ornithine decarboxylase (ODC). Ornithine is a substrate for ODC; decarboxylation of ornithine is inhibited by difluoromethylornithine (DFMO) and its derivatives. Polyamine contents are increased in many epithelial cancers, including breast cancer, melanoma, and prostate cancer. In order to image and measure the levels of ODC expression in malignant tumors, we have synthesized a derivative of ornithine, N5‐[18F]fluoroacetylornithine (N5‐[18F]FAO), for use in positron emission tomography. The precursor compound N2‐Boc‐N5‐bromoacetylornithine‐t‐butyl ester 2 was synthesized from 5‐amino‐2‐(tert‐butoxycarbonylamino)pentanoic acid, which was reacted with bromoacetyl chloride followed by esterification with tert‐butyl‐2,2,2‐trichloroacetamidate. Fluorination of the precursor produced a fluoro‐derivative, which was hydrolyzed in acid to obtain the desired compound, N5‐fluoroacetylornithine. The radiosynthesis of N5‐[18F]FAO was accomplished by radiofluorination of 2 with n‐Bu4N[18F], followed by high‐performance liquid chromatography (HPLC) purification and then by acid hydrolysis. The radiochemical yield was 6–10% (decay corrected) with an average of 8% (n=10) at the end of synthesis. The radiochemical purity was >99%, and specific activity was >1500 mCi/µmol. The synthesis time was 95–100 min from the end of bombardment. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献