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931.
The human colon carcinoma cell line, Caco-2, is the only intestinal cell line to spontaneously differentiate in culture to a population exhibiting structural and biochemical characteristics of mature enterocytes. We conducted studies to establish the presence of the vitamin D receptor (VDR), determine changes in VDR concentration and affinity with differentiation and determine whether 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) mediates a functional response in this cell line. We found that Caco-2 cells possess a specific 1,25(OH)2D3 binding protein similar to the mammalian VDR. It has an equilibrium dissociation constant (Kd) of 0.72 nM, binds vitamin D analogues in order of their biological activities in vivo (1,25(OH)2D3 greater than 25(OH)D3 greater than 24,25(OH)2D3), sediments as a single peak on sucrose density gradients at 3.7 S, and is eluted from a DNA-cellulose column by 0.16 M KCl. The maximum number of binding sites was 2.6-fold greater in the differentiated cell (Day 15) compared to the preconfluent, undifferentiated (Day 4) cell (23 fmol/mg protein vs 56 fmol/mg protein). Cell growth was reduced 59% when exposed to 10(-7) M 1,25(OH)2D3 for 8 days. Alkaline phosphatase activity significantly increased in cultures incubated with 10(-8) M 1,25(OH)2D3 for up to 4 days when treatment was started in both undifferentiated cells (Day 5) and differentiated cells (Day 11). These findings suggest that the VDR present in undifferentiated and differentiated Caco-2 cells is functional. Caco-2 cells provide a unique in vitro model to study vitamin D-regulated functions in differentiated mammalian enterocytes. 相似文献
932.
Penile erection is a muscular and vascular event mediated by the autonomic nervous system. The neurophysiology of erection remains poorly understood and controversial, requiring a suitable model for in-vitro studies of erectile function. Such a model, based in the rat whose penile innervation is very similar to man, is described here. The first study using this model considers the influence of systemic blodd pressure (BP) on penile erection. In 33 anaesthetized rats the pelvic and cavernosal nerves were identified and dissected. Supra maximal electrical stimulation was delivered over 1 minute by a train of 1 ms pulses onto the pelvic nerve (10 V, 15 Hz) or the cavernosal nerve (6 V, 10 Hz). Systemic blood pressure and intracavernosal pressure (ICP) were monitored and stored on a computer. As in previous animal models (dog, monkey), four phases of the cavernosal response to neural electrical stimulation were observed: latency, tumescence, full erection, and détumescence. In all rats electrical stimulation of either the pelvic or cavernosal nerves significantly increased intracavernosal pressure. Complete erectile response (rigidity and unfolding of the penis) was only seen with intracavernosal pressures > 95 mm Hg. Intracavernosal pressure increased proportionally with blood preessure during the full erection phase according to the equation ICP=0.94 BP ? 31 mm Hg (r=0.94 BP ? 31 mm Hg (r=0.94) for electrical stimulation of the cavernosal nerve, or the alternative aquation ICP=0.76 BP ? 21 mm Hg (r=0.73) for electrical stimulation of the pelvic nerve. The rat is a readily available model for the study of erection and present obvious advantages over existing models such as the dog, cat and monkey. Cavernosal repsonse to neural stimulation was closely related to arterial blood pressure and the two linear equations presented above should be considered further in studies modifying autonomic neurotransmission as well as in relation to the effects of pharmacological compounds with vasomotor actions on erectile function. 相似文献
933.
S Sgambato A Ceriello N Passariello D Giuliano 《Biochemistry and experimental biology》1979,15(1):61-64
Plasma Sorbitol Dehydrogenase levels were determined in subjects with diabetes mellitus and normal people. The diabetic subjects had circulating plasma levels of SDH significantly higher (p less than 0.001) than those observed in controls. Moreover, the diabetics with vascular complications presented the highest SDH values. The lack of positive correlation between plasma glucose and SDH levels suggests that SDH, like hemoglobin A1C, reflect the degree of previous metabolic control of diabetes mellitus. 相似文献
934.
Ludvik M. Gomulski Cristina Torti Mariangela Bonizzoni Daniela Moralli Elena Raimondi Pierre Capy Giuliano Gasperi Anna R. Malacrida 《Journal of molecular evolution》2001,53(6):597-606
Several copies of highly related transposable elements, Crmar2, Almar1, and Asmar1, are described from the genomes of Ceratitis rosa, Anastrepha ludens, and A. suspensa, respectively. One copy from C. rosa, Crmar2.5, contains a full-length, uninterrupted ORF. All the other copies, from the three species contain a long deletion within the putative ORF. The consensus Crmar2 element has features typical of the mariner/Tc1 superfamily of transposable elements. In particular, the Crmar2 consensus encodes a D,D41D motif, a variant of the D,D34D catalytic domain of mariner elements. Phylogenetic analysis of the relationships of these three elements and other members of the mariner/Tc1 superfamily, based on their encoded amino acid sequences, suggests that they form a new basal subfamily of mariner elements, the rosa subfamily. BLAST analyses identified sequences from other diptera, including Drosophila melanogaster, which appear to be members of the rosa subfamily of mariner elements. Analyses of their molecular evolution suggests that Crmar2 entered the genome of C. rosa in the recent past, a consequence of horizontal transfer. 相似文献
935.
936.
P Arrigo F Giuliano F Scalia S Bisio M Tagliati G Damiani 《Bollettino della Società italiana di biologia sperimentale》1991,67(10-11):923-929
An application of a computational analysis of cDNA sequences is presented in this paper. The goal is the identification of functional domains on sequence data. The results show the capability of this technique to identify a zone of DNA associated with the signal peptide coding region, whose biological function at DNA or RNA level is still unknown. 相似文献
937.
Ceramide glycosylation potentiates cellular multidrug resistance. 总被引:15,自引:0,他引:15
Ceramide glycosylation, through glucosylceramide synthase (GCS), allows cellular escape from ceramide-induced programmed cell death. This glycosylation event confers cancer cell resistance to cytotoxic anticancer agents [Liu, Y. Y., Han, T. Y., Giuliano, A. E., and M. C. Cabot. (1999) J. Biol. Chem. 274, 1140-1146]. We previously found that glucosylceramide, the glycosylated form of ceramide, accumulates in adriamycin-resistant breast carcinoma cells, in vinblastine-resistant epithelioid carcinoma cells, and in tumor specimens from patients showing poor response to chemotherapy. Here we show that multidrug resistance can be increased over baseline and then totally reversed in human breast cancer cells by GCS gene targeting. In adriamycin-resistant MCF-7-AdrR cells, transfection of GCS upgraded multidrug resistance, whereas transfection of GCS antisense markedly restored cellular sensitivity to anthracyclines, Vinca alkaloids, taxanes, and other anticancer drugs. Sensitivity to the various drugs by GCS antisense transfection increased 7- to 240-fold and was consistent with the resumption of ceramide-caspase-apoptotic signaling. GCS targeting had little influence on cellular sensitivity to either 5-FU or cisplatin, nor did it modify P-glycoprotein expression or rhodamine-123 efflux. GCS antisense transfection did enhance rhodamine-123 uptake compared with parent MCF-7-AdrR cells. This study reveals that GCS is a novel mechanism of multidrug resistance and positions GCS antisense as an innovative force to overcome multidrug resistance in cancer chemotherapy. 相似文献