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P W Nathanielsz - One of the best experts on this subject based on the ideXlab platform.
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Changes in prostacyclin synthase in pregnant sheep myometrium, endometrium, and placenta at spontaneous term labor and regulation by estradiol and progesterone.
American journal of obstetrics and gynecology, 1999Co-Authors: P W NathanielszAbstract:Our purpose was to investigate, first, whether there were changes in the abundance of prostacyclin synthase protein in intrauterine tissues of pregnant ewes in association with spontaneous term labor. Second, we examined the effect of either estradiol or progesterone, or both, on regulation of prostacyclin synthase protein abundance in uterine tissues using an ovariectomized nonpregnant sheep model. The abundance of prostacyclin synthase protein was quantified by Western blot analysis in the myometrium, endometrium, and placenta of pregnant ewes in spontaneous term labor (n = 6) and term control ewes not in labor (n = 6). The changes of prostacyclin synthase in the myometrium and endometrium of 20 ovariectomized nonpregnant sheep (n = 5 for each group) were evaluated after treatment with estradiol, progesterone, or both. Prostacyclin synthase protein was present in pregnant and nonpregnant sheep myometrium, endometrium, and placenta at a molecular weight of about 55 kd. At spontaneous term labor the level of prostacyclin synthase decreased in endometrium (P <.05), increased in myometrium (P <.05), and remained unchanged in placenta. Estradiol and progesterone had no effect on prostacyclin synthase protein abundance in nonpregnant ovine endometrium and myometrium. The decrease in prostacyclin synthase in pregnant sheep endometrium during labor may indicate paracrine interactions between the endometrium, the myometrium, fetal membranes, or a combination of these. The significant increase of prostacyclin synthase in pregnant sheep myometrium at spontaneous term labor may contribute to the increased uterine sensitivity to oxytocin or stimulate vasodilatation during labor to increase myometrial blood flow. Neither estradiol nor progesterone at the dosages studied changed prostacyclin synthase expression in the nonpregnant myometrium and endometrium. The molecular mechanism or mechanisms that differentially regulate prostacyclin synthase expression in pregnant uterine tissues merit further study.
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Changes in prostacyclin synthase in pregnant sheep myometrium, endometrium, and placenta at spontaneous term labor and regulation by estradiol and progesterone.
American Journal of Obstetrics and Gynecology, 1999Co-Authors: Xiao Hong, P W NathanielszAbstract:Abstract Objective: Our purpose was to investigate, first, whether there were changes in the abundance of prostacyclin synthase protein in intrauterine tissues of pregnant ewes in association with spontaneous term labor. Second, we examined the effect of either estradiol or progesterone, or both, on regulation of prostacyclin synthase protein abundance in uterine tissues using an ovariectomized nonpregnant sheep model. Study Design: The abundance of prostacyclin synthase protein was quantified by Western blot analysis in the myometrium, endometrium, and placenta of pregnant ewes in spontaneous term labor (n = 6) and term control ewes not in labor (n = 6). The changes of prostacyclin synthase in the myometrium and endometrium of 20 ovariectomized nonpregnant sheep (n = 5 for each group) were evaluated after treatment with estradiol, progesterone, or both. Results: Prostacyclin synthase protein was present in pregnant and nonpregnant sheep myometrium, endometrium, and placenta at a molecular weight of about 55 kd. At spontaneous term labor the level of prostacyclin synthase decreased in endometrium ( P P Conclusions: The decrease in prostacyclin synthase in pregnant sheep endometrium during labor may indicate paracrine interactions between the endometrium, the myometrium, fetal membranes, or a combination of these. The significant increase of prostacyclin synthase in pregnant sheep myometrium at spontaneous term labor may contribute to the increased uterine sensitivity to oxytocin or stimulate vasodilatation during labor to increase myometrial blood flow. Neither estradiol nor progesterone at the dosages studied changed prostacyclin synthase expression in the nonpregnant myometrium and endometrium. The molecular mechanism or mechanisms that differentially regulate prostacyclin synthase expression in pregnant uterine tissues merit further study. (Am J Obstet Gynecol 1999;180:744-9.)
Agnieszka Blitek - One of the best experts on this subject based on the ideXlab platform.
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Prostacyclin synthesis and prostacyclin receptor expression in the porcine corpus luteum: evidence for a luteotropic role in vitro†
Biology of Reproduction, 2018Co-Authors: Magdalena Szymanska, Agnieszka BlitekAbstract:The prostacyclin (prostaglandin I2) signaling system is an essential regulator of vascular homeostasis. Since the corpus luteum is a highly vascularized gland, prostacyclin seems to be crucial for luteal development and function. Although progress has been made in understanding the luteotropic action of prostacyclin in mammals, its role in the porcine corpus luteum remains to be determined. Therefore, studies were conducted to (1) determine profiles of prostacyclin synthase expression and prostacyclin metabolite concentration, as well as prostacyclin G-protein-coupled receptor expression in porcine luteal tissue on days 2 to 16 of the estrous cycle and days 10 to 30 of pregnancy using real-time PCR, western blot, or enzyme immunoassay; and (2) examine the effect of prostacyclin on progesterone synthesis in vitro. To accomplish the second aim, luteal cells were treated with prostacyclin analogs, iloprost and carbaprostacyclin, in the presence or absence of prostacyclin receptor antagonists. The mRNA expression of cytochrome P450 family 11 subfamily A member 1 and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 was analyzed using real-time PCR, while progesterone concentration in culture medium was assessed by radioimmunoassay.Dynamic changes of prostacyclin synthase and prostacyclin receptor expression were observed in porcine luteal tissue during the estrous cycle and early pregnancy. Moreover, prostacyclin stimulated progesterone production and this effect was abolished by the addition of prostacyclin receptor antagonists. Our findings provide strong evidence that prostacyclin and its signaling system are present in corpus luteum of the pig and may directly promote luteotropic activity through upregulation of progesterone synthesis.Summary SentenceProstacyclin and its receptor system may promote luteotropic action through stimulation of luteal progesterone production.
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Prostacyclin synthesis and prostacyclin receptor expression in the porcine corpus luteum: evidence for a luteotropic role in vitro†
Biology of reproduction, 2018Co-Authors: Magdalena Szymanska, Agnieszka BlitekAbstract:The prostacyclin (prostaglandin I2) signaling system is an essential regulator of vascular homeostasis. Since the corpus luteum is a highly vascularized gland, prostacyclin seems to be crucial for luteal development and function. Although progress has been made in understanding the luteotropic action of prostacyclin in mammals, its role in the porcine corpus luteum remains to be determined. Therefore, studies were conducted to (1) determine profiles of prostacyclin synthase expression and prostacyclin metabolite concentration, as well as prostacyclin G-protein-coupled receptor expression in porcine luteal tissue on days 2 to 16 of the estrous cycle and days 10 to 30 of pregnancy using real-time PCR, western blot, or enzyme immunoassay; and (2) examine the effect of prostacyclin on progesterone synthesis in vitro. To accomplish the second aim, luteal cells were treated with prostacyclin analogs, iloprost and carbaprostacyclin, in the presence or absence of prostacyclin receptor antagonists. The mRNA expression of cytochrome P450 family 11 subfamily A member 1 and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 was analyzed using real-time PCR, while progesterone concentration in culture medium was assessed by radioimmunoassay.Dynamic changes of prostacyclin synthase and prostacyclin receptor expression were observed in porcine luteal tissue during the estrous cycle and early pregnancy. Moreover, prostacyclin stimulated progesterone production and this effect was abolished by the addition of prostacyclin receptor antagonists. Our findings provide strong evidence that prostacyclin and its signaling system are present in corpus luteum of the pig and may directly promote luteotropic activity through upregulation of progesterone synthesis.
Tadashi Tanabe - One of the best experts on this subject based on the ideXlab platform.
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Gene transfer of human prostacyclin synthase into the liver is effective for the treatment of pulmonary hypertension in rats.
The Journal of thoracic and cardiovascular surgery, 2002Co-Authors: Hitoshi Suhara, Chieko Yokoyama, Tadashi Tanabe, Yoshiki Sawa, Norihide Fukushima, Koji Kagisaki, Shigeaki Ohtake, Hikaru MatsudaAbstract:Abstract Background: As one of the future strategies of advanced pulmonary hypertension, intrinsic prostacyclin drug delivery using gene therapy may be useful. We investigated whether transfer of the prostacyclin synthase gene into the liver could ameliorate monocrotaline-induced pulmonary hypertension in rats. Methods: The human prostacyclin synthase gene was transfected into the liver of rats with monocrotaline-induced pulmonary hypertension. Hemodynamic indices, blood samples, lung tissues, and survival curves were evaluated between rats receiving the gene and control rats. Results: High levels of prostacyclin synthase gene expression were found in the hepatocytes of the prostacyclin synthase group. The level of 6-keto-prostaglandin F 1α was significantly higher in the prostacyclin synthase group (prostacyclin synthase, 35.4 ± 4.4 ng/mL; control, 22.3 ± 3.3 ng/mL; P = .0436). The right ventricular/femoral artery pressure ratio was significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 0.60 ± 0.039; control, 0.88 ± 0.051; P = .0036). The endothelin-1 levels in the lung tissues were significantly lower in the prostacyclin synthase group than in the control group (prostacyclin synthase, 10.42 ± 2.01 pg/mg protein; control, 19.94 ± 2.82 pg/mg protein; P = .0176). The survival ratio was significantly higher in the prostacyclin synthase group than the control group ( P = .0375). Conclusion: This drug delivery system using gene transfer can be considered as an alternative for continuous intravenous prostacyclin infusion for pulmonary hypertension. J Thorac Cardiovasc Surg 2002;123:855-61
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Prostacyclin-dependent Apoptosis Mediated by PPARδ
The Journal of biological chemistry, 2001Co-Authors: Toshihisa Hatae, Chieko Yokoyama, Masayuki Wada, Manabu Shimonishi, Tadashi TanabeAbstract:Prostacyclin (PGI(2)) plays important roles in hemostasis both as a vasodilator and an endogenous inhibitor of platelet aggregation. PGI(2) functions in these roles through a specific IP receptor, a G protein-coupled receptor linked to G(s) and increases in cAMP. Here, we report that intracellular prostacyclin formed by expressing prostacyclin synthase in human embryonic kidney 293 cells promotes apoptosis by activating endogenous peroxisome proliferator-activated receptor delta (PPAR delta). In contrast, treatment of cells with extracellular prostacyclin or dibutyryl cAMP actually reduced apoptosis. On the contrary, treatment of the cells with RpcAMP (adenosine 3',5'-cyclic monophosphothioate, Rp-isomer), an antagonist of cAMP, enhanced prostacyclin-mediated apoptosis. The expression of an L431A/G434A mutant of PPAR delta completely blocked prostacyclin-mediated PPAR delta activation and apoptosis. These observations indicate that prostacyclin can act through endogenous PPAR delta as a second signaling pathway that controls cell fate.
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Molecular Cloning of Prostacyclin Synthase from Bovine Endothelial Cells
Advances in experimental medicine and biology, 1997Co-Authors: Tadashi Tanabe, Shuntaro Hara, A. Miyata, R. Brugger, Volker UllrichAbstract:Prostaglandin endoperoxide PGH2 is at the crossroads of arachidonate metabolism, for it is the precursor of substances with opposing biological properties, thromboxane A2 and prostacyclin. Thromboxane A2 produced from PGH2 by the platelets is a powerful contractor of large blood-vessels and induces platelet aggregation. On the other hand, prostacyclin produced from PGH2 by the vessel wall is a powerful vasodilator and the most potent natural occurring inhibitor of platelet aggregation. An imbalance in the thromboxane A2: prostacyclin ratio may provide an explanation as to some of the changes occurring in various pathological situations including thrombosis and ischemia (1). The rearrangement of PGH2 to thromboxane A2 and prostacyclin is catalyzed by thromboxane synthase and prostacyclin synthase, respectively. New approaches to the therapy of such diseases are being sought by developing drugs that tilt the balance in favor of prostacyclin, either by inhibiting thromboxane synthase or protecting prostacyclin synthase. However, the molecular mechanism of these enzyme reactions still remain to be elucidated.
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Molecular Cloning and Expression of Human Prostacyclin Synthase
Biochemical and biophysical research communications, 1994Co-Authors: A. Miyata, Shuntaro Hara, Chieko Yokoyama, Hiroyasu Inoue, Tadashi TanabeAbstract:The cDNA for human prostacyclin synthase was cloned by polymerase chain reaction using poly(A)+ RNA from human aortic endothelial cells according to the partial nucleotide sequence of prostacyclin synthase gene. The cloned cDNA with a size of 1977 base pairs contained a 1500 base pairs open reading frame which encoded a 500 amino acid protein sharing an 88% identity with bovine prostacyclin synthase. RNA blot analysis indicated that the size of major prostacyclin synthase mRNA of human aortic endothelial cells was approximately 6 kilobases and that its mRNA level was increased by interleukin 1 or interleukin 6 treatment. Moreover, tissue distribution study demonstrated that prostacyclin synthase mRNA is widely expressed in human tissues and is particularly abundant in ovary, heart, skeletal muscle, lung, and prostate. These results suggest a variety of physiological roles of prostacyclin in addition to the implications in the cardiovascular system.
Magdalena Szymanska - One of the best experts on this subject based on the ideXlab platform.
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Prostacyclin synthesis and prostacyclin receptor expression in the porcine corpus luteum: evidence for a luteotropic role in vitro†
Biology of Reproduction, 2018Co-Authors: Magdalena Szymanska, Agnieszka BlitekAbstract:The prostacyclin (prostaglandin I2) signaling system is an essential regulator of vascular homeostasis. Since the corpus luteum is a highly vascularized gland, prostacyclin seems to be crucial for luteal development and function. Although progress has been made in understanding the luteotropic action of prostacyclin in mammals, its role in the porcine corpus luteum remains to be determined. Therefore, studies were conducted to (1) determine profiles of prostacyclin synthase expression and prostacyclin metabolite concentration, as well as prostacyclin G-protein-coupled receptor expression in porcine luteal tissue on days 2 to 16 of the estrous cycle and days 10 to 30 of pregnancy using real-time PCR, western blot, or enzyme immunoassay; and (2) examine the effect of prostacyclin on progesterone synthesis in vitro. To accomplish the second aim, luteal cells were treated with prostacyclin analogs, iloprost and carbaprostacyclin, in the presence or absence of prostacyclin receptor antagonists. The mRNA expression of cytochrome P450 family 11 subfamily A member 1 and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 was analyzed using real-time PCR, while progesterone concentration in culture medium was assessed by radioimmunoassay.Dynamic changes of prostacyclin synthase and prostacyclin receptor expression were observed in porcine luteal tissue during the estrous cycle and early pregnancy. Moreover, prostacyclin stimulated progesterone production and this effect was abolished by the addition of prostacyclin receptor antagonists. Our findings provide strong evidence that prostacyclin and its signaling system are present in corpus luteum of the pig and may directly promote luteotropic activity through upregulation of progesterone synthesis.Summary SentenceProstacyclin and its receptor system may promote luteotropic action through stimulation of luteal progesterone production.
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Prostacyclin synthesis and prostacyclin receptor expression in the porcine corpus luteum: evidence for a luteotropic role in vitro†
Biology of reproduction, 2018Co-Authors: Magdalena Szymanska, Agnieszka BlitekAbstract:The prostacyclin (prostaglandin I2) signaling system is an essential regulator of vascular homeostasis. Since the corpus luteum is a highly vascularized gland, prostacyclin seems to be crucial for luteal development and function. Although progress has been made in understanding the luteotropic action of prostacyclin in mammals, its role in the porcine corpus luteum remains to be determined. Therefore, studies were conducted to (1) determine profiles of prostacyclin synthase expression and prostacyclin metabolite concentration, as well as prostacyclin G-protein-coupled receptor expression in porcine luteal tissue on days 2 to 16 of the estrous cycle and days 10 to 30 of pregnancy using real-time PCR, western blot, or enzyme immunoassay; and (2) examine the effect of prostacyclin on progesterone synthesis in vitro. To accomplish the second aim, luteal cells were treated with prostacyclin analogs, iloprost and carbaprostacyclin, in the presence or absence of prostacyclin receptor antagonists. The mRNA expression of cytochrome P450 family 11 subfamily A member 1 and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 was analyzed using real-time PCR, while progesterone concentration in culture medium was assessed by radioimmunoassay.Dynamic changes of prostacyclin synthase and prostacyclin receptor expression were observed in porcine luteal tissue during the estrous cycle and early pregnancy. Moreover, prostacyclin stimulated progesterone production and this effect was abolished by the addition of prostacyclin receptor antagonists. Our findings provide strong evidence that prostacyclin and its signaling system are present in corpus luteum of the pig and may directly promote luteotropic activity through upregulation of progesterone synthesis.
Malak Alyamani - One of the best experts on this subject based on the ideXlab platform.
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cyclooxygenase 1 not cyclooxygenase 2 is responsible for physiological production of prostacyclin in the cardiovascular system
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Nicholas S. Kirkby, Martina H Lundberg, Louise S Harrington, P D M Leadbeater, Ginger L Milne, Claire M F Potter, Malak AlyamaniAbstract:Prostacyclin is an antithrombotic hormone produced by the endothelium, whose production is dependent on cyclooxygenase (COX) enzymes of which two isoforms exist. It is widely believed that COX-2 drives prostacyclin production and that this explains the cardiovascular toxicity associated with COX-2 inhibition, yet the evidence for this relies on indirect evidence from urinary metabolites. Here we have used a range of experimental approaches to explore which isoform drives the production of prostacyclin in vitro and in vivo. Our data show unequivocally that under physiological conditions it is COX-1 and not COX-2 that drives prostacyclin production in the cardiovascular system, and that urinary metabolites do not reflect prostacyclin production in the systemic circulation. With the idea that COX-2 in endothelium drives prostacyclin production in healthy individuals removed, we must seek new answers to why COX-2 inhibitors increase the risk of cardiovascular events to move forward with drug discovery and to enable more informed prescribing advice.
