The Experts below are selected from a list of 22440 Experts worldwide ranked by ideXlab platform
Michael E. Disanto - One of the best experts on this subject based on the ideXlab platform.
-
Regional heterogeneity in expression of the Sphingosine-1-Phosphate pathway in the female rat lower urinary tract.
American Journal of Obstetrics and Gynecology, 2009Co-Authors: Katherine S Sandhu, Rowena G Chua, Nirmala Devi Kanika, Magdy Mikhail, Sarah A. Collins, Arnold Melman, Xinhua Zhang, Michael E. DisantoAbstract:Objective We investigated the existence and regional distribution of Sphingosine-1-Phosphate regulatory enzymes and receptors in the lower urinary tract and determined the functional role of Sphingosine-1-Phosphate receptors in the bladder. Study Design Lower urinary tract tissue from 10 female rats was harvested for real-time reverse transcriptase-polymerase chain reaction or organ bath physiology, whereas blood serum was obtained for high-performance liquid chromatography determination of Sphingosine-1-Phosphate levels. Statistical analysis included the Student t test and analysis of variance. Results All 3 Sphingosine-1-Phosphate receptors and major enzymes were expressed throughout the lower urinary tract, but expression and physiologic force generation varied among regions. Sphingosine-1-Phosphate was detected in serum. Conclusion We provide novel data that the Sphingosine-1-Phosphate signaling pathway regulatory proteins exist throughout the female rat lower urinary tract, but that relative expression exhibits regional heterogeneity corresponding with lower urinary tract contractile response to Sphingosine-1-Phosphate. Our study suggests that Sphingosine-1-Phosphate signaling is important in the lower urinary tract and identifies this pathway as a possible target for altering bladder smooth muscle tone.
-
Regional heterogeneity in expression of the Sphingosine-1-Phosphate pathway in the female rat lower urinary tract.
American journal of obstetrics and gynecology, 2009Co-Authors: Katherine S Sandhu, Rowena G Chua, Nirmala Devi Kanika, Magdy Mikhail, Sarah A. Collins, Arnold Melman, Xinhua Zhang, Michael E. DisantoAbstract:We investigated the existence and regional distribution of Sphingosine-1-Phosphate regulatory enzymes and receptors in the lower urinary tract and determined the functional role of Sphingosine-1-Phosphate receptors in the bladder. Lower urinary tract tissue from 10 female rats was harvested for real-time reverse transcriptase-polymerase chain reaction or organ bath physiology, whereas blood serum was obtained for high-performance liquid chromatography determination of Sphingosine-1-Phosphate levels. Statistical analysis included the Student t test and analysis of variance. All 3 Sphingosine-1-Phosphate receptors and major enzymes were expressed throughout the lower urinary tract, but expression and physiologic force generation varied among regions. Sphingosine-1-Phosphate was detected in serum. We provide novel data that the Sphingosine-1-Phosphate signaling pathway regulatory proteins exist throughout the female rat lower urinary tract, but that relative expression exhibits regional heterogeneity corresponding with lower urinary tract contractile response to Sphingosine-1-Phosphate. Our study suggests that Sphingosine-1-Phosphate signaling is important in the lower urinary tract and identifies this pathway as a possible target for altering bladder smooth muscle tone.
Osamu Kozawa - One of the best experts on this subject based on the ideXlab platform.
-
Involvement of Rho-kinase in Sphingosine 1-Phosphate-stimulated HSP27 induction in osteoblasts
International Journal of Molecular Medicine, 2009Co-Authors: Chiho Minamitani, Yoshiteru Hanai, Jun Mizutani, Shinji Takai, Haruhiko Tokuda, Rie Matsushima-nishiwaki, Takanobu Otsuka, Seiji Adachi, Osamu KozawaAbstract:We previously reported that Sphingosine 1-Phosphate induces heat shock protein 27 (HSP 27) via activation of phosphatidylinositol 3-kinase (PI3K)/Akt and p38 mitogen- activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is implicated in Sphingosine 1-Phosphate-stimulated induction of HSP27 in MC3T3-E1 cells. Sphingosine 1-Phosphate time- dependently induced the phosphorylation of myosin phos- phatase targeting subunit (MYPT-1), a Rho-kinase substrate. Y27632, a specific Rho-kinase inhibitor, significantly reduced Sphingosine 1-Phosphate-stimulated HSP27 induction, as well as MYPT-1 phosphorylation. Fasudil, another inhibitor of Rho- kinase, also suppressed Sphingosine 1-Phosphate-stimulated HSP27 induction. Y27632, as well as fasudil, attenuated Sphingosine 1-Phosphate-induced phosphorylation of p38 MAP kinase. However, Akt phosphorylation induced by Sphingosine 1-Phosphate was not affected by either Rho-kinase inhibitor. These results strongly suggest that Rho-kinase regulates Sphingosine 1-Phosphate-stimulated induction of HSP27 at a point upstream of p38 MAP kinase in osteoblasts.
-
Phosphatidylinositol 3-kinase/Akt plays a role in Sphingosine 1-Phosphate-stimulated HSP27 induction in osteoblasts
Journal of Cellular Biochemistry, 2006Co-Authors: Shinji Takai, Yoshiteru Hanai, Kanefusa Kato, Haruhiko Tokuda, Rie Matsushima-nishiwaki, Osamu KozawaAbstract:We previously reported that p38 mitogen-activated protein (MAP) kinase plays a part in Sphingosine 1-Phosphate-stimulated heat shock protein 27 (HSP27) induction in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) is involved in the induction of HSP27 in these cells. Sphingosine 1-Phosphate time dependently induced the phosphorylation of Akt. Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, reduced the HSP27 induction stimulated by Sphingosine 1-Phosphate. The Sphingosine 1-Phosphate-induced phosphorylation of GSK-3β was suppressed by Akt inhibitor. The Sphingosine 1-Phosphate-induced HSP27 levels were attenuated by LY294002 or wortmannin, PI3K inhibitors. Furthermore, LY294002 or Akt inhibitor did not affect the Sphingosine 1-Phosphate-induced phosphorylation of p38 MAP kinase and SB203580, a p38 MAP kinase inhibitor, had little effect on the phosphorylation of Akt. These results suggest that PI3K/Akt plays a part in the Sphingosine 1-Phosphate-stimulated induction of HSP27, maybe independently of p38 MAP kinase, in osteoblasts. J. Cell. Biochem. 98: 1249–1256, 2006. © 2006 Wiley-Liss, Inc.
-
Phosphatidylinositol 3-kinase/Akt plays a role in Sphingosine 1-Phosphate-stimulated HSP27 induction in osteoblasts.
Journal of cellular biochemistry, 2006Co-Authors: Shinji Takai, Yoshiteru Hanai, Kanefusa Kato, Haruhiko Tokuda, Rie Matsushima-nishiwaki, Osamu KozawaAbstract:We previously reported that p38 mitogen-activated protein (MAP) kinase plays a part in Sphingosine 1-Phosphate-stimulated heat shock protein 27 (HSP27) induction in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) is involved in the induction of HSP27 in these cells. Sphingosine 1-Phosphate time dependently induced the phosphorylation of Akt. Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, reduced the HSP27 induction stimulated by Sphingosine 1-Phosphate. The Sphingosine 1-Phosphate-induced phosphorylation of GSK-3beta was suppressed by Akt inhibitor. The Sphingosine 1-Phosphate-induced HSP27 levels were attenuated by LY294002 or wortmannin, PI3K inhibitors. Furthermore, LY294002 or Akt inhibitor did not affect the Sphingosine 1-Phosphate-induced phosphorylation of p38 MAP kinase and SB203580, a p38 MAP kinase inhibitor, had little effect on the phosphorylation of Akt. These results suggest that PI3K/Akt plays a part in the Sphingosine 1-Phosphate-stimulated induction of HSP27, maybe independently of p38 MAP kinase, in osteoblasts.
-
Sphingosine 1-Phosphate amplifies phosphoinositide hydrolysis stimulated by prostaglandin F2α in osteoblasts: involvement of p38 MAP kinase
Prostaglandins Leukotrienes and Essential Fatty Acids, 2000Co-Authors: Osamu Kozawa, Hidenori Kawamura, Toshihiko UematsuAbstract:We previously showed that Sphingosine 1-Phosphate phosphorylates p42/p44 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Sphingosine 1-Phosphate on phospholipase C-catalyzing phosphoinositide hydrolysis induced by prostaglandin F2α (PGF2α) in these cells. Sphingosine 1-Phosphate significantly amplified the inositol Phosphates formation by PGF2α. Sphingosine 1-Phosphate did not enhance the formation induced by NaF, a direct activator of heterotrimeric GTP-binding proteins. PD98059, an inhibitor of the kinase that activates p42/p44 MAP kinase, had little effect on the amplification by Sphingosine 1-Phosphate. SB203580, an inhibitor of p38 MAP kinase, reduced the effect of Sphingosine 1-Phosphate on the formation of inositol Phosphates by PGF2α. The phosphorylation of p42/p44 MAP kinase by PGFα was attenuated by PD98059. SB203580 suppressed the phosphorylation of p38 MAP kinase by PGF2α. Tumor necrosis factor-α enhanced the PGF2α-stimulated formation of inositol Phosphates. These results strongly suggest that Sphingosine 1-Phosphate amplifies PGF2α-induced phosphoinositide hydrolysis by phospholipase C through p38 MAP kinase in osteoblasts.
-
Sphingosine 1-Phosphate induces heat shock protein 27 via p38 mitogen-activated protein kinase activation in osteoblasts.
Journal of Bone and Mineral Research, 1999Co-Authors: Osamu Kozawa, Masaichi Miwa, Kanefusa Kato, Haruhiko Tokuda, Masayuki Niwa, Hiroyuki Matsuno, Toshihiko UematsuAbstract:We previously showed that Sphingosine 1-Phosphate acts as a second messenger for tumor necrosis factor α–induced interleukin-6 synthesis in osteoblast-like MC3T3-E1 cells and that the synthesis by Sphingosine 1-Phosphate is dependent on p42/p44 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated the effect of Sphingosine 1-Phosphate on the induction of heat shock protein 27 (HSP27) in MC3T3-E1 cells. Not C2-ceramide, but Sphingosine and Sphingosine 1-Phosphate significantly induced HSP27 accumulation dose dependently in the range between 1μM and 30 μM. DL-threo-dihydroSphingosine, an inhibitor of Sphingosine kinase, markedly inhibited the Sphingosine-induced HSP27 accumulation. Sphingosine 1-Phosphate induced increase in the levels of the mRNA for HSP27. Sphingosine 1-Phosphate stimulated the phosphorylation of p38 MAP kinase. The Sphingosine 1-Phosphate–induced HSP27 accumulation was dose dependently suppressed by SB203580, an inhibitor of p38 MAP kinase, but not PD98059, an inhibitor of the upstream kinase that activates p42/p44 MAP kinase. SB203580 reduced the Sphingosine 1-Phosphate–induced increase of mRNA for HSP27. These results strongly suggest that Sphingosine 1-Phosphate–stimulated HSP27 induction is mediated via p38 MAP kinase activation in osteoblasts.
Julie D Saba - One of the best experts on this subject based on the ideXlab platform.
-
An update on Sphingosine-1-Phosphate and other sphingolipid mediators
Nature Chemical Biology, 2010Co-Authors: Henrik Fyrst, Julie D SabaAbstract:Sphingolipids comprise a complex family of naturally occurring molecules that are enriched in lipid rafts and contribute to their unique biochemical properties. Membrane sphingolipids also serve as a reservoir for bioactive metabolites including Sphingosine, ceramide, Sphingosine-1-Phosphate and ceramide-1-Phosphate. Among these, Sphingosine-1-Phosphate has emerged as a central regulator of mammalian biology. Sphingosine-1-Phosphate is essential for mammalian brain and cardiac development and for maturation of the systemic circulatory system and lymphatics. In addition, Sphingosine-1-Phosphate contributes to trafficking and effector functions of lymphocytes and other hematopoietic cells and protects against various forms of tissue injury. However, Sphingosine-1-Phosphate is also an oncogenic lipid that promotes tumor growth and progression. Recent preclinical and clinical investigations using pharmacological agents that target Sphingosine-1-Phosphate, its receptors and the enzymes required for its biosynthesis and degradation demonstrate the promise and potential risks of modulating Sphingosine-1-Phosphate signaling in treatment strategies for autoimmunity, cancer, cardiovascular disease and other pathological conditions.
-
Sphingosine 1-Phosphate lyase enzyme assay using a BODIPY-labeled substrate
Biochemical and Biophysical Research Communications, 2009Co-Authors: Padmavathi Bandhuvula, Zaiguo Li, Robert Bittman, Julie D SabaAbstract:Abstract Sphingosine 1-Phosphate lyase (SPL) is responsible for the irreversible catabolism of Sphingosine 1-Phosphate, which signals through five membrane receptors to mediate cell stress responses, angiogenesis, and lymphocyte trafficking. The standard assay for SPL activity utilizes a radioactive dihydroSphingosine 1-Phosphate substrate and is expensive and cumbersome. In this study, we describe an SPL assay that employs an ω-labeled BODIPY–Sphingosine 1-Phosphate substrate, allowing fluorescent product detection by HPLC and incorporating advantages of the BODIPY fluorophore. The major aldehyde product is confirmed by reaction with 2,4-dinitrophenylhydrazine. The SPL-catalyzed reaction is linear over a 30 min time period and yields a Km of 35 μM for BODIPY–Sphingosine 1-Phosphate.
-
Sphingosine 1-Phosphate lyase enzyme assay using a BODIPY-labeled substrate
Biochemical and biophysical research communications, 2009Co-Authors: Padmavathi Bandhuvula, Robert Bittman, Julie D SabaAbstract:Sphingosine 1-Phosphate lyase (SPL) is responsible for the irreversible catabolism of Sphingosine 1-Phosphate, which signals through five membrane receptors to mediate cell stress responses, angiogenesis, and lymphocyte trafficking. The standard assay for SPL activity utilizes a radioactive dihydroSphingosine 1-Phosphate substrate and is expensive and cumbersome. In this study, we describe an SPL assay that employs an omega-labeled BODIPY-Sphingosine 1-Phosphate substrate, allowing fluorescent product detection by HPLC and incorporating advantages of the BODIPY fluorophore. The major aldehyde product is confirmed by reaction with 2,4-dinitrophenylhydrazine. The SPL-catalyzed reaction is linear over a 30 min time period and yields a K(m) of 35 microM for BODIPY-Sphingosine 1-Phosphate.
-
Sphingosine-1-Phosphate Lyase
Sphingolipid Biology, 2006Co-Authors: Julie D SabaAbstract:Sphingosine-1-Phosphate lyase is responsible for the ultimate step in sphingolipid degradation. Sphingosine-1-Phosphate and other phosphorylated long chain bases generated through the actions of Sphingosine kinase may be dephosphorylated by lipid phosphatases or cleaved at the C2–3 carbon-carbon bond by the pyridoxal 5’-Phosphate-dependent enzyme, Sphingosine-1-Phosphate lyase. By regulating intracellular levels of phosphorylated long chain bases, Sphingosine-1-Phosphate lyase may control intracellular and extracellular signaling events mediated by these bioactive molecules. Through additional effects mediated by its substrate and products on the biosynthesis of sphingolipids, their conversion into phospholipids, and the synthesis of sterols and fatty acids, Sphingosine-1-Phosphate lyase may regulate the flow of lipid intermediates through several metabolic pathways. Subsequent to the cloning of the first Sphingosine-1-Phosphate lyase gene from Saccharomyces cerevisiae, putative homologs have been identified in various plant and animal species, indicating that the enzyme is highly conserved. Sphingosine-1-Phosphate lyase mutant phenotypes in fungi, simple metazoans, and mammalian cells suggest that the enzyme plays a role in the regulation of apoptosis, stress responses, reproduction, development, and tissue integrity and repair. Analysis of Sphingosine-1-Phosphate lyase gene expression has shed light on how the enzyme may be regulated under physiological conditions. Identification of specific inhibitors and generation of constitutive and conditional mouse knockout models should facilitate the dissection of Sphingosine-1-Phosphate lyase’s role within the context of mammalian development, physiology and the pathophysiology of various disease states.
-
The immune modulator FTY720 inhibits Sphingosine-1-Phosphate lyase activity
Journal of Biological Chemistry, 2005Co-Authors: Padmavathi Bandhuvula, Babak Oskouian, Julie D SabaAbstract:Abstract FTY720 is a novel immunomodulatory agent that inhibits lymphocyte trafficking and prevents allograft rejection. FTY720 is phosphorylated in vivo, and the phosphorylated drug acts as agonist for a family of G protein-coupled receptors that recognize Sphingosine 1-Phosphate. Evidence suggests that FTY720-Phosphate-induced activation of S1P1 is responsible for its mechanism of action. FTY720 was rationally designed by modification of myriocin, a naturally occurring sphingoid base analog that causes immunosuppression by interrupting sphingolipid metabolism. In this study, we examined interactions between FTY720, FTY720-Phosphate, and Sphingosine-1-Phosphate lyase, the enzyme responsible for irreversible Sphingosine 1-Phosphate degradation. FTY720-Phosphate was stable in the presence of active Sphingosine-1-Phosphate lyase, demonstrating that the lyase does not contribute to FTY720 catabolism. Conversely, FTY720 inhibited Sphingosine-1-Phosphate lyase activity in vitro. Treatment of mice with FTY720 inhibited tissue Sphingosine-1-Phosphate lyase activity within 12 h, whereas lyase gene and protein expression were not significantly affected. Tissue Sphingosine 1-Phosphate levels remained stable or increased throughout treatment. These studies raise the possibility that disruption of Sphingosine 1-Phosphate metabolism may account for some effects of FTY720 on immune function and that Sphingosine-1-Phosphate lyase may be a potential target for immunomodulatory therapy.
Sarah Spiegel - One of the best experts on this subject based on the ideXlab platform.
-
Structure of the First Sphingosine 1-Phosphate Receptor
Science Signaling, 2012Co-Authors: Abby L Parrill, Santiago Lima, Sarah SpiegelAbstract:The Sphingosine 1-Phosphate receptor 1 (S1P 1 ) and its ligand, Sphingosine 1-Phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. S1P 1 is targeted by the phosphorylation product of fingolimod, which has been approved for the treatment of multiple sclerosis. The recent progress in the structural biology of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors has now enabled the elucidation of the structure of S1P 1 . Analysis of the structure, along with structure activity and mutagenesis analysis, highlighted key interactions associated with the binding of S1P and agonists and suggested that the ligand may gain access to the binding pocket by lateral diffusion within the plasma membrane. The S1P 1 crystal structure will be helpful for designing ligands that specifically target S1P 1 .
-
Sphingosine 1 Phosphate an enigmatic signalling lipid
Nature Reviews Molecular Cell Biology, 2003Co-Authors: Sarah Spiegel, Sheldon MilstienAbstract:The evolutionarily conserved actions of the sphingolipid metabolite, Sphingosine-1-Phosphate (S1P), in yeast, plants and mammals have shown that it has important functions. In higher eukaryotes, S1P is the ligand for a family of five G-protein-coupled receptors. These S1P receptors are differentially expressed, coupled to various G proteins, and regulate angiogenesis, vascular maturation, cardiac development and immunity, and are important for directed cell movement.
-
Suppression of ceramide-mediated programmed cell death by Sphingosine-1-Phosphate
Nature, 1996Co-Authors: Olivier Cuvillier, Philip G. Vanek, Grisha Pirianov, Omar A Coso, J. Silvio Gutkind, Burkhard Kleuser, Sarah SpiegelAbstract:CERAMIDE is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-α and Fas ligand, members of the TNF superfamily1–6. Conversely, Sphingosine and Sphingosine-1-Phosphate, which are metabolites of ceramide, induce mitogenesis7 and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor and serum8,9. Here we report that Sphingosine-1-Phosphate prevents the appearance of the key features of apoptosis, namely intranucleosomal DNA fragmentation and morphological changes, which result from increased concentrations of ceramide. Furthermore, inhibition of ceramide-mediated apoptosis by activation of protein kinase C results from stimulation of Sphingosine kinase and the concomitant increase in intracellular Sphingosine-1-Phosphate. Finally Sphingosine-1-Phosphate not only stimulates the extracellular signal-regulated kinase (ERK) pathway10, it counteracts the ceramide-induced activation of stress-activated protein kinase (SAPK/JNK). Thus, the balance between the intracellular levels of ceramide and Sphingosine-1-Phosphate and their regulatory effects on different family members of mitogen-activated protein kineses determines the fate of the cell.
-
Suppression of ceramide-mediated programmed cell death by Sphingosine-1-Phosphate.
Nature, 1996Co-Authors: Olivier Cuvillier, Philip G. Vanek, Grisha Pirianov, Omar A Coso, J. Silvio Gutkind, Burkhard Kleuser, Sarah SpiegelAbstract:Ceramide is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-alpha and Fas ligand, members of the TNF superfamily. Conversely, Sphingosine and Sphingosine-1-Phosphate, which are metabolites of ceramide, induce mitogenesis and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor and serum. Here we report that Sphingosine-1-Phosphate prevents the appearance of the key features of apoptosis, namely intranucleosomal DNA fragmentation and morphological changes, which result from increased concentrations of ceramide. Furthermore, inhibition of ceramide-mediated apoptosis by activation of protein kinase C results from stimulation of Sphingosine kinase and the concomitant increase in intracellular Sphingosine-1-Phosphate. Finally Sphingosine-1-Phosphate not only stimulates the extracellular signal-regulated kinase (ERK) pathway, it counteracts the ceramide-induced activation of stress-activated protein kinase (SAPK/JNK). Thus, the balance between the intracellular levels of ceramide and Sphingosine-1-Phosphate and their regulatory effects on different family members of mitogen-activated protein kinases determines the fate of the cell.
-
Sphingosine 1-Phosphate rapidly activates the mitogen-activated protein kinase pathway by a G protein-dependent mechanism
Journal of Biological Chemistry, 1995Co-Authors: Jie Wu, Sarah Spiegel, Thomas W SturgillAbstract:Abstract Addition of Sphingosine 1-Phosphate induces proliferation of quiescent Swiss 3T3 fibroblasts by unknown mechanisms. To identify the pathways involved, the ability of Sphingosine 1-Phosphate to activate mitogen- activated protein (MAP) kinase was studied. Sphingosine 1-Phosphate rapidly activated the Raf/MAP kinase kinase (MKK)/MAP kinase pathway, and the concentration dependence for MAP kinase activation correlated with that for induction of DNA synthesis. Both MKK1 and MKK2 were activated by Sphingosine 1-Phosphate, assessed by specific immune complex kinase assays. Prior treatment of the Swiss 3T3 cells with pertussis toxin inhibited 70-80% of the Sphingosine 1-Phosphate- stimulated MAP kinase activity. Thus, one of the direct or indirect targets of exogenous Sphingosine 1-Phosphate appears to be a G(i)/G(o) protein.
Katherine S Sandhu - One of the best experts on this subject based on the ideXlab platform.
-
Regional heterogeneity in expression of the Sphingosine-1-Phosphate pathway in the female rat lower urinary tract.
American Journal of Obstetrics and Gynecology, 2009Co-Authors: Katherine S Sandhu, Rowena G Chua, Nirmala Devi Kanika, Magdy Mikhail, Sarah A. Collins, Arnold Melman, Xinhua Zhang, Michael E. DisantoAbstract:Objective We investigated the existence and regional distribution of Sphingosine-1-Phosphate regulatory enzymes and receptors in the lower urinary tract and determined the functional role of Sphingosine-1-Phosphate receptors in the bladder. Study Design Lower urinary tract tissue from 10 female rats was harvested for real-time reverse transcriptase-polymerase chain reaction or organ bath physiology, whereas blood serum was obtained for high-performance liquid chromatography determination of Sphingosine-1-Phosphate levels. Statistical analysis included the Student t test and analysis of variance. Results All 3 Sphingosine-1-Phosphate receptors and major enzymes were expressed throughout the lower urinary tract, but expression and physiologic force generation varied among regions. Sphingosine-1-Phosphate was detected in serum. Conclusion We provide novel data that the Sphingosine-1-Phosphate signaling pathway regulatory proteins exist throughout the female rat lower urinary tract, but that relative expression exhibits regional heterogeneity corresponding with lower urinary tract contractile response to Sphingosine-1-Phosphate. Our study suggests that Sphingosine-1-Phosphate signaling is important in the lower urinary tract and identifies this pathway as a possible target for altering bladder smooth muscle tone.
-
Regional heterogeneity in expression of the Sphingosine-1-Phosphate pathway in the female rat lower urinary tract.
American journal of obstetrics and gynecology, 2009Co-Authors: Katherine S Sandhu, Rowena G Chua, Nirmala Devi Kanika, Magdy Mikhail, Sarah A. Collins, Arnold Melman, Xinhua Zhang, Michael E. DisantoAbstract:We investigated the existence and regional distribution of Sphingosine-1-Phosphate regulatory enzymes and receptors in the lower urinary tract and determined the functional role of Sphingosine-1-Phosphate receptors in the bladder. Lower urinary tract tissue from 10 female rats was harvested for real-time reverse transcriptase-polymerase chain reaction or organ bath physiology, whereas blood serum was obtained for high-performance liquid chromatography determination of Sphingosine-1-Phosphate levels. Statistical analysis included the Student t test and analysis of variance. All 3 Sphingosine-1-Phosphate receptors and major enzymes were expressed throughout the lower urinary tract, but expression and physiologic force generation varied among regions. Sphingosine-1-Phosphate was detected in serum. We provide novel data that the Sphingosine-1-Phosphate signaling pathway regulatory proteins exist throughout the female rat lower urinary tract, but that relative expression exhibits regional heterogeneity corresponding with lower urinary tract contractile response to Sphingosine-1-Phosphate. Our study suggests that Sphingosine-1-Phosphate signaling is important in the lower urinary tract and identifies this pathway as a possible target for altering bladder smooth muscle tone.