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1.
《Prostaglandins and medicine》1981,6(4):345-357
Regiospecific monomethyl prostaglandin F2α ethers (at 0–9, 0–11, and 0–15) have been prepared by total synthesis. The 9,15-bis-ether was also prepared. The 11- and 15-monoethers have been converted to the corresponding prostacyclins. Nuclear Magnetic Resonance (NMR) spectral comparisons indicate conformational changes associated with ether formation; nonetheless, the PGF2α monoethers all retain significant biological activity: 3–420% of natural PGF2α. The 9- and 15-methyl ethers show increased selectivity for luteolytic activity as measured in the hamster antifertility (HAF) assay. In contrast the prostacyclin ethers are essentially devoid of agonist activity on both the platelet and vasculature. Prostacyclin diastereomers [5a] also lack activity and it appears that any modification at or of the C-11 or C-15 functions reduces receptor binding by at least a factor of 100. 相似文献
2.
《Animal reproduction science》1987,14(2):103-113
Six cyclic Holstein dairy cows were anesthetized on days 12–14 post-oestrus. Reproductive tract was exposed by midventral incision, and the ovarian (utero-ovarian) vein and facial artery cannulated. Oviduct was ligated, and a catheter (affluent) introduced into the tip of the uterine horn. The uterine horn was ligated above the uterine body, a second catheter (effluent) introduced into the uterine lumen, and an electromagnetic blood flow transducer placed around the uterine artery. On the day following surgery, the uterine horn was infused constantly for 9 h with PGF2α dissolved in PBS (0.7 ml/min, 177 ng/ml). During periods 1 and 3 (first 3 h and last 3 h, respectively) only PGF2α was perfused; during period 2 (between 3 h and 6 h) 101tgμg/ml of PGE2 were added to the perfusate together with PGF2α. Uterine venous and peripheral blood samples were collected simultaneously every 15 min, and uterine blood flow recorded continuously. Least-square means for PGF measured in uterine venous drainage for periods 1, 2 and 3 were 315 ± 26, 557 ± 24 and 511 ± 26 pg/ml, respectively (P < 0.05). Uterine blood flow values were 52 ± 5, 67 ± 4 and 61 ± 4 ml/min for periods 1, 2 and 3 (P < 0.08), respectively.Results do not support the hypothesis that the antiluteolytic effect of PGE2 is associated with a suppression of uterine PGF2α release into the circulation. Greater release of PGF to the circulation in period 2 (addition of PGE2) is probably the result of the vasodilatory effect of PGE2 on uterine endometrial vasculature. 相似文献
3.
Basu Samar Kindahl Hans Harvey Denis Betteridge Keith J. 《Acta veterinaria Scandinavica》1987,28(3-4):409-420
The metabolism of PGF2α in cattle results initially in the formation of 15-keto-13,14-dihydro-PGF2α (15-ketodihydro-PGF2α) and later the 11-ketotetranor PGF metabolites. Both types of metabolites appear in the peripheral circulation and finally the 11-ketotetranor PGF metabolites are found in large quantities in the urine in a species-related pattern. Several approaches can be made to the quantitative analysis of PGF2α release during reproductive studies. First, assay of the 15-ketodihydro-PGF2α metabolite in the peripheral circulation; second, analysis of the longer-lived 11-ketotetranor PGF metabolites in the peripheral circulation; and finally analysis of the latter metabolites in the urine. The antibodies used in radioimmunoassays of both types of metabolites of PGF2α were found to be specific and the results agree well with those obtained earlier by mass spectrometric analysis. The assay of 11-ketotetranor PGF metabolites was used to study the excretion of urinary metabolites in the cow after i.v. infusion of PGF2α and also during the normal estrous cycle and early pregnancy. These studies suggest that 11-ketotetranor PGF metabolites in cow urine serve as a good parameter of PGF2α release, especially for long–term studies, but when a precise pattern of PGF2α release is required, measurement of 15-ketodihydro-PGF2α levels in frequently collected plasma samples is preferable. 相似文献
4.
《Small Ruminant Research》2007,68(2-3):257-263
Prostaglandin E2 has been shown to increase the ovine embryo hatching rate, and PGF2α to reduce the development of rabbit, bovine, and rat embryos. The objective was to determine the effects of PGE2 and PGF2α on development of caprine embryos. Estrus was synchronized in does (n = 25) with medroxyprogesterone acetate (MAP) intravaginal sponges for 12 days, and superovulated with 20 units of FSH. On day 6 following estrus, embryos were flushed (n = 128) and incubated individually per well in 25 μl droplets of TCM-199 and BSA (8 mg/ml) for 6 days at 38.5 °C in a 5% CO2: air with one of the following treatments: (1) control (0.0002% EtOH), (2) PGE2 (7 ng/ml), (3) PGF2α (7 ng/ml), (4) low PGE2:high PGF2α (3.5 ng/ml:14 ng/ml), (5) balanced PGE2:PGF2α (7 ng/ml:7 ng/ml), or (6) high PGE2:low PGF2α (14 ng/ml:3.5 ng/ml). Treatment with PGE2 alone reduced (P < 0.05) the hatching rate (1/15; 7%). The hatching rate of embryos treated with PGF2α alone (9/18; 50%), low PGE2:high PGF2α (8/16; 50%), and balanced PGE2:PGF2α (11/16; 69%) were similar to control (6/18; 33%). In contrast, the hatching rate was non-significantly increased (13/18; 72%) with the high PGE2:low PGF2α treatment. None of the treatments affected development from the morula to blastocyst stage. From the current data, it can be concluded that PGE2 alone reduced hatching rate, and PGF2α alone had no effect on the development of caprine embryos. High concentrations of PGE2 with PGF2α improved the hatching rates. Thus, uterine concentrations of PGE2 may need to reach a threshold level to improve embryo hatching, as previously reported, while increased uterine concentrations of PGF2α during early pregnancy would not affect development of the embryo. 相似文献
5.
The effect of prostaglandins F2 and E2 on unit activity and sensitivity of somatosensory cortical neurons of rabbits to acetylcholine and noradrenalin was investigated by microiontophoresis. Prostaglandin F2 predominantly inhibited, whereas E2 increased the spike activity of the neurons. F2 usually modified the sensitivity of the neurons to acetylcholine, E2 to noradrenalin. The influence of F2 on the excitatory effects of acetylcholine, and of E2 on the inhibitory effects of noradrenalin as a rule was characterized by weakening of the action of the mediators or a change in the sign of the initial responses. It is suggested that prostaglandins of the F group participate in cholinergic, and those of the E group in adrenergic transmission. The prostaglandins studied evidently exert their action through selective inhibition of the activity of adenylate or guanylate cyclases, leading to a decrease in the synthesis of secondary transmitters, namely cyclic AMP and cyclic GMP.B. K. Anokhin Research Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 3, pp. 239–245, May–June, 1980. 相似文献
6.
Haejin Yoon Seung-Hyun ShinDong Hoon Shin Yang-Sook ChunJong-Wan Park 《Biochemical and biophysical research communications》2014
Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) determine cancer cell fate under hypoxia. Despite the similarities of their structures, HIF-1α and HIF-2α have distinct roles in cancer growth under hypoxia, that is, HIF-1α induces growth arrest whereas HIF-2α promotes cell growth. Recently, sirtuin 1 (Sirt1) was reported to fine-tune cellular responses to hypoxia by deacetylating HIF-1α and HIF-2α. Yet, the roles of Sirt1 in HIF-1α and HIF-2α functions have been controversial. We here investigated the precise roles of Sirt1 in HIF-1α and HIF-2α regulations. Immunological analyses revealed that HIF-1α K674 and HIF-2α K741 are acetylated by PCAF and CBP, respectively, but are deacetylated commonly by Sirt1. In the Gal4 reporter systems, Sirt1 was found to repress HIF-1α activity constantly in ten cancer cell-lines but to regulate HIF-2α activity cell type-dependently. Moreover, Sirt1 determined cell growth under hypoxia depending on HIF-1α and HIF-2α. Under hypoxia, Sirt1 promoted cell proliferation of HepG2, in which Sirt1 differentially regulates HIF-1α and HIF-2α. In contrast, such an effect of Sirt1 was not shown in HCT116, in which Sirt1 inactivates both HIF-1α and HIF-2α because conflicting actions of HIF-1α and HIF-2α on cell growth may be offset. Our results provide a better understanding of the roles of Sirt1 in HIF-mediated hypoxic responses and also a basic concept for developing anticancer strategy targeting Sirt1. 相似文献
7.
Gillies RM Robinson SP McPhail LD Carter ND Murray JF 《Journal of molecular histology》2011,42(4):341-354
Hypoxia is thought to be critical in regulating physiological processes within the female reproductive system, including ovulation,
composition of the fluid in the oviductal/uterine lumens and ovarian follicle development. This study examined the localisation
of exogenous (pimonidazole) and endogenous [hypoxia inducible factor 1α and 2α (HIF1α, -2α), glucose transporter type 1 (GLUT1)
and carbonic anhydrase 9 (CAIX)] hypoxia-related antigens within the oviduct and uterus of the rat reproductive tract. The
extent to which each endogenous antigen co-compartmentalised with pimonidazole was also assessed. Female Wistar Furth rats
(n = 10) were injected intraperitoneally with pimonidazole (60 mg/kg) 1 h prior to death. Reproductive tissues were removed
immediately following death and fixed in 4% paraformaldehyde before being embedded in paraffin. Serial sections were cut (6–7 μm
thick) and antigens of interest identified using standard immunohistochemical procedures. The mucosal epithelia of the ampulla,
isthmus and uterus were immunopositive for pimonidazole in most sections. Co-compartmentalisation of pimonidazole with HIF1α
was only expressed in the mucosa of the uterus whilst co-compartmentalisation with HIF2α was observed in the mucosa of the
ampulla, isthmus and uterus. Both GLUT1 and CAIX were co-compartmentalised with pimonidazole in mucosa of the isthmus and
uterus. This study confirms that mucosal regions of the rat oviduct and uterus frequently experience severe hypoxia and there
are compartment specific variations in expression of endogenous hypoxia-related antigens, including the HIF isoforms. The
latter observation may relate to target gene specificity of HIF isoforms or perhaps HIF2α’s responsiveness to non-hypoxic
stimuli such as hypoglycaemia independently of HIF1α. 相似文献
8.
9.
《Biochemical medicine》1982,27(1):26-36
Prostaglandins E2 and F2α have regulatory roles, respectively, in the potentiation and inhibition of erythropoietin. Antisera to PGF2α and EIF, an erythropoiesis inhibitory factor, can be used to resolve the reason for improvement in erythropoiesis following renal dialysis. Concurrent loss of PGE2 with Ep during treatment with neuraminidase suggests that PGE2 is bound to Ep by way of sialic acid. 相似文献
10.
11.
Flunixin meglumine (FM; 2.5 mg/kg) was given to heifers at three 8-h intervals, 16 d after ovulation (first treatment = Hour 0) to inhibit the synthesis of prostaglandin F2α (PGF), based on plasma concentrations of a PGF metabolite (PGFM). Blood samples were collected at 8-h intervals from 15 to 18 d in a vehicle (control) and FM group (n = 16/group). Hourly samples were collected from Hours −2 to 28 in 10 heifers in each group. Heifers that were in preluteolysis or luteolysis at Hour 0 based on plasma progesterone (P4) concentrations at 8-h intervals were partitioned into subgroups. Concentration of PGFM was reduced (P < 0.05) by FM treatment in each subgroup. For the preluteolytic subgroup, the first decrease (P < 0.05) in P4 concentration after Hour 0 occurred at Hours 24 and 40 in the vehicle and FM groups, respectively. Plasma P4 concentrations 32 and 40 h after the beginning of luteolysis in the luteolytic subgroup were greater (P < 0.05) in the FM group. Concentration at the peak of a PGFM pulse in the FM group was greater (P < 0.05) in the luteolytic than in the preluteolytic subgroup. The peak of a PGFM pulse occurred more frequently (P < 0.001) at the same hour as the peak of an LH fluctuation than at the ending nadir of an LH fluctuation. In conclusion, a reduction in prominence of PGFM pulses during luteolysis delayed completion of luteolysis, and treatment with FM inhibited PGFM production more during preluteolysis than during luteolysis. 相似文献
12.
13.
Experiments were carried out in healthy male volunteers to investigate the effect of the inhalation of prostaglandin F2α (PGF2α) on airways resistance and the influence of the subsequent inhalation of prostaglandin E2 (PGE2). Airways resistance, which reflects the tone of smooth muscle in the larger airways in man, was measured by total body plethysmography.The inhalation of PGF2α (40-60 μg) caused an increase in airways resistance in all subjects. Both PGE2 (55 μg) and isoprenaline (550 μg) given by metered aerosol promptly reversed the bronchoconstriction induced by PGF2α, but isoprenaline was more effective in this respect.A role for these prostaglandins in the control of bronchial muscle tone is discussed. 相似文献
14.
Takeshi Nakajima Emi Nakajima Thomas R. Shearer Mitsuyoshi Azuma 《Molecular and cellular biochemistry》2013,383(1-2):113-122
HIF-1α is known to play an important role in the induction of VEGF by hypoxia in retinal pigment epithelial (RPE) cells. However, the involvement of the other isoform, HIF-2α, in RPE cells remains unclear. Thus, the purpose of present study was to clarify the role of HIF-2α during induction of angiogenic genes in hypoxic RPE cells. When human RPE cells (ARPE-19) were cultured under hypoxic conditions, HIF-1α and HIF-2α proteins increased. This induced an increase in mRNA for VEGF, causing secretion of VEGF protein into the medium. This conditioned medium induced tube formation in human vascular endothelial cells (HUVEC). The increased expression of mRNA for VEGF in hypoxic RPE cells was partially inhibited by HIF-1α siRNA, but not by HIF-2α siRNA. However, co-transfection of HIF-1α siRNA and HIF-2α siRNA augmented downregulation of VEGF mRNA and protein in hypoxic RPE cells and inhibited formation of tube-like structures in HUVEC. GeneChip and PCR array analyses revealed that not only VEGF, but also expression of other angiogenic genes were synergistically downregulated by co-transfection of hypoxic RPE cells with HIF-1α and HIF-2α siRNAs. These findings suggest an important compensatory role for the HIF-2α isoform in the regulation of angiogenic gene expression. Thus, suppression of angiogenic genes for HIF-1α and HIF-2α may be a possible therapeutic strategy against retinal angiogenesis in Age-related macular degeneration (ARMD). 相似文献
15.
Marie Naveau Christine Lazennec-Schurdevin Michel Panvert Etienne Dubiez Yves Mechulam Emmanuelle Schmitt 《Nucleic acids research》2013,41(2):1047-1057
Heterotrimeric eukaryotic/archaeal translation initiation factor 2 (e/aIF2) binds initiator methionyl-tRNA and plays a key role in the selection of the start codon on messenger RNA. tRNA binding was extensively studied in the archaeal system. The γ subunit is able to bind tRNA, but the α subunit is required to reach high affinity whereas the β subunit has only a minor role. In Saccharomyces cerevisiae however, the available data suggest an opposite scenario with β having the most important contribution to tRNA-binding affinity. In order to overcome difficulties with purification of the yeast eIF2γ subunit, we designed chimeric eIF2 by assembling yeast α and β subunits to archaeal γ subunit. We show that the β subunit of yeast has indeed an important role, with the eukaryote-specific N- and C-terminal domains being necessary to obtain full tRNA-binding affinity. The α subunit apparently has a modest contribution. However, the positive effect of α on tRNA binding can be progressively increased upon shortening the acidic C-terminal extension. These results, together with small angle X-ray scattering experiments, support the idea that in yeast eIF2, the tRNA molecule is bound by the α subunit in a manner similar to that observed in the archaeal aIF2–GDPNP–tRNA complex. 相似文献
16.
17.
《Prostaglandins and medicine》1979,2(6):425-431
Ovulation induced by HCG in rabbits was blocked by a single subcutaneous injection of 6 mg/kg indomethacin given 6 h after the insemination and HCG treatment. In addition, a time-dependent inhibition in the fertilization rate after indomethacin treatment was also recorded. This suggests that indomethacin, when given at a critical time and at an appropriate dose level, not only blocks ovulation but also interferes with fertilization.Treatment with graded amounts of prostaglandin-F2α incorporated in a Silastic-polyvinylpyrrolidone-gel (PVP) had marginal to no effect after intravaginal placement on 4- or 6-day pregnancy. However, 5 mg PGF2α Silastic-PVP tube when placed intravaginally on Day-7 of pregnancy resulted in termination of pregnancy in 66% of the treated does. This implies that young corpora lutea are resistant to PGF2α treatment and that pregnancy at the time of ovo-implantation can be terminated by PGF2α incorporated in a Silastic-PVP tube. 相似文献
18.
Augusto Diaz-Infante Karen H. Wright Edward E. Wallach 《Prostaglandins & other lipid mediators》1974,5(6):567-581
The present investigation was carried out to determine whether inhibition of ovulation in the rabbit by administration of indomethacin can be correlated with any change in ovarian contractility at ovulation time and can be reversed by administration of prostaglandins. Indomethacin was adminstered intra-muscularly using three different schedules in a dose of 5 mg/kg. A reduced number of ruptured follicles following HCG was noted in all groups treated with indomethacin. Infusion of PGF2α into the aorta (1 μg/kg/min.) could reverse this effect. Less pronounced ovarian contractility was observed after indomethacin treatment, but infusion of PGF2α immediately enhanced contractility in ovaries from indomethacin treated rabbits. The inhibition of ovulation in the rabbit associated with indomethacin adminstration may be related to suppression of ovarian contractions. These data also suggest that prostaglandins may play a significant role in the mechanism of ovulation through an influence on ovarian contractility. 相似文献
19.
Raaf J Bischoff N Klopffleisch K Brunstein E Olsen BB Vilk G Litchfield DW Issinger OG Niefind K 《Biochemistry》2011,50(4):512-522
The protein Ser/Thr kinase CK2 (former name: casein kinase II) exists predominantly as a heterotetrameric holoenzyme composed of two catalytic subunits (CK2α) bound to a dimer of noncatalytic subunits (CK2β). We undertook a study to further understand how these subunits interact to form the tetramer. To this end, we used recombinant, C-terminal truncated forms of human CK2 subunits that are able to form the holoenzyme. We analyzed the interaction thermodynamics between the binding of CK2α and CK2β as well as the impact of changes in temperature, pH, and the ionization enthalpy of the buffer using isothermal titration calorimetry (ITC). With structure-guided alanine scanning mutagenesis we truncated individual side chains in the hydrophobic amino acid cluster located within the CK2α interface to identify experimentally the amino acids that dominate affinity. The ITC results indicate that Leu41 or Phe54 single mutations were most disruptive to binding of CK2β. Additionally, these CK2α mutants retained their kinase activity. Furthermore, the substitution of Leu41 in combination with Phe54 showed that the individual mutations were not additive, suggesting that the cooperative action of both residues played a role. Interestingly, the replacement of Ile69, which has a central position in the interaction surface of CK2α, only had modest effects. The differences between Leu41, Phe54, and Ile69 in interaction relevance correlate with solvent accessibility changes during the transition from unbound to CK2β-bound CK2α. Identifying residues on CK2α that play a key role in CK2α/CK2β interactions is important for the future generation of small molecule drug design. 相似文献