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1.
Localization of Drug-Metabolizing Enzyme Activities to Blood-Brain Interfaces and Circumventricular Organs 总被引:3,自引:2,他引:1
J. F. Ghersi-Egea B. Leninger-Muller G. Suleman G. Siest A. Minn 《Journal of neurochemistry》1994,62(3):1089-1096
Abstract: The brain, with the exception of the choroid plexuses and Circumventricular organs, is partially protected from the invasion of blood-borne chemicals by the specific morphological properties of the cerebral micro-vessels, namely, the tight junctions of the blood-brain barrier. Recently, several enzymes that are primarily involved in hepatic drug metabolism have been shown to exist in the brain, albeit at relatively low specific activities. In the present study, the hypothesis that these enzymes are located primarily at blood-brain interfaces, where they form an "enzymatic barrier," is tested. By using microdissection techniques or a gradient-centrifugation isolation procedure, the activities of seven drug-metabolizing enzymes in isolated microvessels, choroid plexuses, meningeal membranes, and tissue from three Circumventricular organs (the neural lobe of the hypophysis, pineal gland, and median eminence) were assayed. With two exceptions, the activities of these enzymes were higher in the three Circumventricular organs and cerebral microvessel than in the cortex. Very high membrane-bound epoxide hydrolase and UDP-glucuronosyltransferase activities (approaching those in liver) and somewhat high 7-benzoxyre-sorufin- O -dealkylase and NADPH-cytochrome P-450 reductase activities were determined in the choroid plexuses. The pia-arachnoid membranes, but not the dura matter, displayed drug-metabolizing enzyme activities, notably that of epoxide hydrolase: The drug-metabolizing enzymes located at these nonparenchymal sites may function to protect brain tissue from harmful compounds. 相似文献
2.
B Walther J F Ghersi-Egea A Minn G Siest 《Archives of biochemistry and biophysics》1987,254(2):592-596
The cytochrome P-450-dependent cholesterol side chain cleavage system of the brain has been studied using nonsynaptic mitochondria as the source of enzymatic activity. The system has been found to bind cholesterol and 11-deoxycorticosterone, producing type I difference spectra, whereas the binding of pregnenolone induced a reverse type I difference spectrum. Inhibitors of cytochrome P-450-linked monooxygenase activities produced type II spectra. The formation of labeled pregnenolone after incubation of brain mitochondria with [4-14C]cholesterol has been obtained, and this formation was inhibited by glutethimide, a specific inhibitor of cytochrome P-450scc. The functional significance of this enzymatic activity is discussed. 相似文献
3.
4.
Genetic variation of teak (Tectona grandis Linn. f.) in 16 populations in Myanmar was investigated using ten nuclear microsatellite markers. Eight population pairs from two main regions in the north and the south of Myanmar were sampled. Each population pair consisted of an unlogged and a recently logged forest, each represented by 50 adult trees and 50 seedlings from the natural regeneration. For comparison, two land races from Benin (West Africa) were included. The major objectives of the study are to characterize the patterns of genetic variation of teak in natural populations, to examine genetic differentiation between adult trees and natural regeneration, and to investigate the impact of selective logging on genetic structures of teak. Genetic variation was high in all investigated populations. Slightly elevated levels of inbreeding were observed in the regeneration in comparison to the adults. Populations from the northern and the southern regions were strongly differentiated, but the differentiation between adults and natural regeneration and between unlogged and logged forests was low and not significant. Mantel tests indicated an isolation by distance (IBD) within the northern and the southern regions. High genetic diversity was also observed within the land races from Benin, which grouped to the southern populations. We failed to detect effects of logging on genetic diversity patterns or inbreeding in adults and regeneration, suggesting that high genetic diversity can even be sampled and maintained in disturbed forests. The observation of significant IBD and high differentiation between the populations of the north and the south of Myanmar suggests to include populations from widely separated forests in conservation programs, and to delineate provenance regions for the harvest and transfer of teak seeds and seedlings. 相似文献
5.
Andy J. Minn Elena Bevilacqua Jieun Yun Marsha Rich Rosner 《Cell cycle (Georgetown, Tex.)》2012,11(13):2452-2457
Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. Given the heterogeneity of mutations in cancer cells, considerable focus has been directed toward characterizing metastasis genes in the context of relevant signaling pathways rather than treating genes as independent and equal entities. One signaling cascade implicated in the regulation of cell growth, invasion and metastasis is the MAP kinase pathway. Raf kinase inhibitory protein (RKIP) functions as an inhibitor of the MAP kinase pathway and is a metastasis suppressor in different cancer models. By utilizing statistical analysis of clinical data integrated with experimental validation, we recently identified components of the RKIP signaling pathway relevant to breast cancer metastasis. Using the RKIP pathway as an example, we show how prior biological knowledge can be efficiently combined with genome-wide patient data to identify gene regulatory mechanisms that control metastasis. 相似文献
6.
Adenosine Transport into Guinea-pig Synaptosomes 总被引:2,自引:15,他引:2
Abstract: Kinetics for transport of adenosine into guinea-pig neocortex synaptosomes were studied by incubating them with [14 C]adenosine for up to 30 s. The apparent K m value of the high-affinity transport system for adenosine was 21.1 μM and the V max value was 257.3 pmol/min/mg protein. The transport system was inhibited by both compounds structurally related (compounds 554 and 555) and unrelated (dipyridamole) to adenosine. Because electrically stimulated synaptosomes release up to 1.5% of the adenosine derivative content per min, the physiological significance of adenosine uptake is discussed as a possible mechanism to compensate for the loss of adenine nucleotides from synaptosomes preparations. 相似文献
7.
The effect of myofibroblast on contracture of hypertrophic scar 总被引:14,自引:0,他引:14
Wound contraction in humans has both positive and negative effects. It is beneficial to wound healing by narrowing the wound margins, but the formation of undesirable scar contracture brings cosmetic and even functional problems. The entire mechanism of wound healing and scar contracture is not clear yet, but it is at least considered that both the fibroblasts and the myofibroblasts are responsible for contraction in healing wounds. The myofibroblast is a cell that possesses all the morphologic and biochemical characteristics of both a fibroblast and a smooth muscle cell. Normally, the myofibroblasts appear in the initial wound healing processes and generate contractile forces to pull both edges of an open wound until it disappears by apoptosis. But as an altered regulation of myofibroblast disappearance, they remain in the dermis and continuously contract the scar, eventually causing scar contracture. In this research, to compare and directly evaluate the influence on scar contracture of the myofibroblast versus the fibroblast, dermal tissues were taken from 10 patients who had highly contracted hypertrophic scars. The myofibroblasts were isolated and concentrated from the fibroblasts using the magnetic activating cell-sorting column to obtain the myofibroblast group, which contained about 28 to 41 percent of the myofibroblasts, and the fibroblast group, which contained less than 0.9 percent of the myofibroblasts. Each group was cultured in the fibroblast-populated collagen lattice for 13 days, and the contraction of the collagen gel was measured every other day. In addition, they were selectively treated with tranilast [N-(3',4'-dimethoxycinnamoyl) anthranilic acid] to evaluate the influence on the contraction of the collagen gel lattice. During the culture, the myofibroblast group, compared with the fibroblast group, showed statistically significant contraction of the collagen gel lattice day by day, except on the first day, and only the myofibroblast group was affected by tranilast treatment, showing significant inhibition of gel contraction. By utilizing an in vitro model, the authors have demonstrated that myofibroblasts play a more important role in the contracture of the hypertrophic scar. 相似文献
8.
Apomorphine, a dopaminergic receptor agonist, is largely used in the therapy of Parkinson's disease. In this study, we characterized the glucuronidation of apomorphine and other catechols in rat liver and brain microsomes, using UDP-[U-14C]glucuronic acid and separation of the glucuronides formed by a thin layer chromatographic method. rat liver microsomes glucuronidate apomorphine at a significant rate, that was increased in the presence of dithiothreitol. Two apomorphine glucuronides were separated by high pressure liquid chromatography. We showed by electrospray mass spectrometry that both products were monoglucuronides. Other catechols were also glucuronidated in liver microsomes at various rates, and among them, 4-nitrocatechol was the most efficiently conjugated. in rat brain microsomes, only 4-nitrocatechol was significantly glucuronidated, suggesting that in the liver, several uridine-diphosphate glucuronosyltransferase (UGT) isoforms participate to the conjugation of catechols. To determine which isoforms catalyze apomorphine glucuronidation, two recombinant enzymes expressed in V79 cells were used. The isoform UGT1A6 was unable to glucuronidate apomorphine, but we observed a significant activity catalyzed by the isoform UGT2B1. These results provide, to our knowledge, the first demonstration of apomorphine conjugation by recombinant UGT2B1, and the first evidence of the lack of apomorphine glucuronidation in the rat brain. 相似文献
9.
p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice 总被引:2,自引:0,他引:2 下载免费PDF全文
53BP1 is a p53 binding protein of unknown function that binds to the central DNA-binding domain of p53. It relocates to the sites of DNA strand breaks in response to DNA damage and is a putative substrate of the ataxia telangiectasia-mutated (ATM) kinase. To study the biological role of 53BP1, we disrupted the 53BP1 gene in the mouse. We show that, similar to ATM(-/-) mice, 53BP1-deficient mice were growth retarded, immune deficient, radiation sensitive, and cancer prone. 53BP1(-/-) cells show a slight S-phase checkpoint defect and prolonged G(2)/M arrest after treatment with ionizing radiation. Moreover, 53BP1(-/-) cells feature a defective DNA damage response with impaired Chk2 activation. These data indicate that 53BP1 acts downstream of ATM and upstream of Chk2 in the DNA damage response pathway and is involved in tumor suppression. 相似文献
10.
Kotilainen P Airas L Kojo T Kurki T Kataja K Minn H Nuutila P 《Neuro endocrinology letters》2005,26(1):67-68
Our patient developed Riedel's thyroiditis soon after having an exacerbation of multiple sclerosis (MS). MS has been associated with other autoimmune diseases, including thyroiditis, and both Hashimoto's thyroiditis and subacute thyroiditis have been described in connection with MS. Yet, we are not aware of any other patient reported to have concomitant MS and Riedel's thyroiditis. The association between MS and Riedel's thyroiditis remains obscure but may reflect an autoimmune disorder common to both diseases. 相似文献