The Experts below are selected from a list of 30588 Experts worldwide ranked by ideXlab platform
Nateetip Krishnamra - One of the best experts on this subject based on the ideXlab platform.
-
fibroblast growth factor 23 negates 1 25 oh 2d3 induced intestinal Calcium Transport by reducing the transcellular and paracellular Calcium fluxes
Archives of Biochemistry and Biophysics, 2013Co-Authors: Pissared Khuituan, Nateetip Krishnamra, Walailuk Jantarajit, Kannikar Wongdee, Panan Suntornsaratoon, Narattaphol CharoenphandhuAbstract:Abstract The calciotropic hormone 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has been known to stimulate intestinal Calcium Transport via both transcellular and paracellular pathways. Recently, we reported that the 1,25(OH) 2 D 3 -enhanced Calcium Transport in the mouse duodenum could be abolished by fibroblast growth factor (FGF)-23, but the targeted Calcium Transport pathway has been elusive. Herein, the 1,25(OH) 2 D 3 -enhanced Calcium Transport was markedly inhibited by FGF-23 and inhibitors of the basolateral Calcium Transporters, NCX1 and PMCA 1b , suggesting the negative effect of FGF-23 on the transcellular Calcium Transport. Similar results could be observed in the intestinal epithelium-like Caco-2 monolayer. Although the Arrhenius plot indicated that FGF-23 decreased the potential barrier (e.g., activation energy) of the paracellular Calcium movement, FGF-23 was found to modestly decrease the 1,25(OH) 2 D 3 -enhanced paracellular Calcium Transport and Calcium permeability. Moreover, FGF-23 affected the 1,25(OH) 2 D 3 -induced change in duodenal water permeability as determined by tritiated water, but both 1,25(OH) 2 D 3 and FGF-23 were without effects on the transepithelial fluxes of paracellular markers, 3 H-mannitol and 14 C-polyethylene glycol. It could be concluded that FGF-23 diminished the 1,25(OH) 2 D 3 -enhanced Calcium absorption through the transcellular and paracellular pathways. Our findings have thus corroborated the presence of a bone–kidney–intestinal axis of FGF-23/vitamin D system in the regulation of Calcium homeostasis.
-
Transepithelial Calcium Transport in prolactin-exposed intestine-like Caco-2 monolayer after combinatorial knockdown of TRPV5, TRPV6 and Ca_v1.3
The Journal of Physiological Sciences, 2009Co-Authors: La-iad Nakkrasae, Narongrit Thongon, Jirawan Thongbunchoo, Nateetip Krishnamra, Narattaphol CharoenphandhuAbstract:The milk-producing hormone prolactin (PRL) increases the transcellular intestinal Calcium absorption by enhancing apical Calcium uptake through voltage-dependent L-type Calcium channel (Ca_v) 1.3. However, the redundancy of apical Calcium channels raised the possibility that Ca_v1.3 may operate with other channels, especially transient receptor potential vanilloid family Calcium channels (TRPV) 5 or 6, in an interdependent manner. Herein, TRPV5 knockdown (KD), TRPV5/TRPV6, TRPV5/Ca_v1.3, and TRPV6/Ca_v1.3 double KD, and TRPV5/TRPV6/Ca_v1.3 triple KD Caco-2 monolayers were generated by transfecting cells with small interfering RNAs (siRNA). siRNAs downregulated only the target mRNAs, and did not induce compensatory upregulation of the remaining channels. After exposure to 600 ng/mL PRL, the transcellular Calcium Transport was increased by ~2-fold in scrambled siRNA-treated, TRPV5 KD and TRPV5/TRPV6 KD monolayers, but not in TRPV5/Ca_v1.3, TRPV6/Ca_v1.3 and TRPV5/TRPV6/Ca_v1.3 KD monolayers. The results suggested that Ca_v1.3 was the sole apical channel responsible for the PRL-stimulated transcellular Calcium Transport in intestine-like Caco-2 monolayer.
-
direct stimulation of the transcellular and paracellular Calcium Transport in the rat cecum by prolactin
Pflügers Archiv: European Journal of Physiology, 2009Co-Authors: Kamonshanok Kraidith, La-iad Nakkrasae, Nateetip Krishnamra, Walailuk Jantarajit, Jarinthorn Teerapornpuntakit, Narattaphol CharoenphandhuAbstract:Prolactin (PRL) is reported to stimulate Calcium absorption in the rat’s small intestine. However, little is known regarding its effects on the cecum, a part of the large intestine with the highest rate of intestinal Calcium Transport. We demonstrated herein by quantitative real-time polymerase chain reaction and Western blot analysis that the cecum could be a target organ of PRL since cecal epithelial cells strongly expressed PRL receptors. In Ussing chamber experiments, PRL enhanced the transcellular cecal Calcium absorption in a biphasic dose–response manner. PRL also increased the paracellular Calcium permeability and passive Calcium Transport in the cecum, which could be explained by the PRL-induced decrease in transepithelial resistance and increase in cation selectivity of the cecal epithelium. PRL actions in the cecum were abolished by inhibitors of phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), and RhoA-associated coiled-coil forming kinase (ROCK), but not inhibitors of gene transcription and protein biosynthesis. In conclusion, PRL directly enhanced the transcellular and paracellular Calcium Transport in the rat cecum through the nongenomic signaling pathways involving PI3K, PKC, and ROCK.
-
chronic metabolic acidosis stimulated transcellular and solvent drag induced Calcium Transport in the duodenum of female rats
American Journal of Physiology-gastrointestinal and Liver Physiology, 2006Co-Authors: Narattaphol Charoenphandhu, Kukiat Tudpor, Naritsara Pulsook, Nateetip KrishnamraAbstract:Chronic metabolic acidosis results in a negative Calcium balance as a result of bone resorption and renal Calcium loss. However, reports on the changes in intestinal Calcium Transport have been con...
-
long term prolactin exposure differentially stimulated the transcellular and solvent drag induced Calcium Transport in the duodenum of ovariectomized rats
Experimental Biology and Medicine, 2005Co-Authors: Kukiat Tudpor, Narattaphol Charoenphandhu, Wasana Saengamnart, Nateetip KrishnamraAbstract:Prolactin, having been shown to stimulate transcellular active and solvent drag-induced Calcium Transport in the duodenum of female rats, was postulated to improve duodenal Calcium Transport in estrogen-deficient rats. The aim of the present study was, therefore, to demonstrate the effects of long-term prolactin exposure produced by anterior pituitary (AP) trans- plantation on the duodenal Calcium Transport in young (9-week- old) and adult (22-week-old) ovariectomized rats. We found that ovariectomy did not alter the transcellular active duodenal Calcium Transport in young and adult rats fed normal Calcium diet (1.0% w/w Ca) but decreased the solvent drag-induced duodenal Calcium Transport from 75.50 6 10.12 to 55.75 6 4.77 nmolhr � 1 �cm � 2 (P , 0.05) only in adult rats. Long-term prolactin exposure stimulated the transcellular active Calcium Transport in young and adult AP-grafted ovariectomized rats fed with normal Calcium diet by more than 2-fold from 7.56 6 0.79 to 16.54 6 2.05 (P , 0.001) and 9.78 6 0.72 to 15.99 6 1.75 (P , 0.001) nmolhr � 1 �cm � 2 , respectively. However, only the solvent drag- induced duodenal Calcium Transport in young rats was enhanced by prolactin from 95.51 6 10.64 to 163.20 6 18.03 nmolhr � 1 �cm � 2 (P , 0.001) whereas that in adult rats still showed a decreased flux from 75.50 6 10.12 to 47.77 6 5.42 nmolhr � 1 �cm � 2 (P , 0.05). Because oral Calcium supplement has been widely used to improve Calcium balance in estrogen- deficient animals, the effect of a high-Calcium diet (2.0% w/w Ca) was also investigated. The results showed that stimulatory action of long-term prolactin on the transcellular active duodenal Calcium Transport in both young and adult rats was diminished after being fed a high-Calcium diet. The same diet also abolished prolactin-enhanced solvent drag-induced duo- denal Calcium Transport in young and further decreased that in adult AP-grafted ovariectomized rats. We concluded that the solvent drag-induced duodenal Calcium Transport in adult rats was decreased after ovariectomy. Long-term prolactin exposure stimulated the transcellular active duodenal Calcium Transport in both young and adult rats whereas enhancing the solvent drag- induced duodenal Calcium Transport only in young rats. Effects of prolactin were abolished by a high-Calcium diet. Exp Biol Med 230:836-844, 2005.
Narattaphol Charoenphandhu - One of the best experts on this subject based on the ideXlab platform.
-
fibroblast growth factor 23 negates 1 25 oh 2d3 induced intestinal Calcium Transport by reducing the transcellular and paracellular Calcium fluxes
Archives of Biochemistry and Biophysics, 2013Co-Authors: Pissared Khuituan, Nateetip Krishnamra, Walailuk Jantarajit, Kannikar Wongdee, Panan Suntornsaratoon, Narattaphol CharoenphandhuAbstract:Abstract The calciotropic hormone 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has been known to stimulate intestinal Calcium Transport via both transcellular and paracellular pathways. Recently, we reported that the 1,25(OH) 2 D 3 -enhanced Calcium Transport in the mouse duodenum could be abolished by fibroblast growth factor (FGF)-23, but the targeted Calcium Transport pathway has been elusive. Herein, the 1,25(OH) 2 D 3 -enhanced Calcium Transport was markedly inhibited by FGF-23 and inhibitors of the basolateral Calcium Transporters, NCX1 and PMCA 1b , suggesting the negative effect of FGF-23 on the transcellular Calcium Transport. Similar results could be observed in the intestinal epithelium-like Caco-2 monolayer. Although the Arrhenius plot indicated that FGF-23 decreased the potential barrier (e.g., activation energy) of the paracellular Calcium movement, FGF-23 was found to modestly decrease the 1,25(OH) 2 D 3 -enhanced paracellular Calcium Transport and Calcium permeability. Moreover, FGF-23 affected the 1,25(OH) 2 D 3 -induced change in duodenal water permeability as determined by tritiated water, but both 1,25(OH) 2 D 3 and FGF-23 were without effects on the transepithelial fluxes of paracellular markers, 3 H-mannitol and 14 C-polyethylene glycol. It could be concluded that FGF-23 diminished the 1,25(OH) 2 D 3 -enhanced Calcium absorption through the transcellular and paracellular pathways. Our findings have thus corroborated the presence of a bone–kidney–intestinal axis of FGF-23/vitamin D system in the regulation of Calcium homeostasis.
-
Transepithelial Calcium Transport in prolactin-exposed intestine-like Caco-2 monolayer after combinatorial knockdown of TRPV5, TRPV6 and Ca_v1.3
The Journal of Physiological Sciences, 2009Co-Authors: La-iad Nakkrasae, Narongrit Thongon, Jirawan Thongbunchoo, Nateetip Krishnamra, Narattaphol CharoenphandhuAbstract:The milk-producing hormone prolactin (PRL) increases the transcellular intestinal Calcium absorption by enhancing apical Calcium uptake through voltage-dependent L-type Calcium channel (Ca_v) 1.3. However, the redundancy of apical Calcium channels raised the possibility that Ca_v1.3 may operate with other channels, especially transient receptor potential vanilloid family Calcium channels (TRPV) 5 or 6, in an interdependent manner. Herein, TRPV5 knockdown (KD), TRPV5/TRPV6, TRPV5/Ca_v1.3, and TRPV6/Ca_v1.3 double KD, and TRPV5/TRPV6/Ca_v1.3 triple KD Caco-2 monolayers were generated by transfecting cells with small interfering RNAs (siRNA). siRNAs downregulated only the target mRNAs, and did not induce compensatory upregulation of the remaining channels. After exposure to 600 ng/mL PRL, the transcellular Calcium Transport was increased by ~2-fold in scrambled siRNA-treated, TRPV5 KD and TRPV5/TRPV6 KD monolayers, but not in TRPV5/Ca_v1.3, TRPV6/Ca_v1.3 and TRPV5/TRPV6/Ca_v1.3 KD monolayers. The results suggested that Ca_v1.3 was the sole apical channel responsible for the PRL-stimulated transcellular Calcium Transport in intestine-like Caco-2 monolayer.
-
direct stimulation of the transcellular and paracellular Calcium Transport in the rat cecum by prolactin
Pflügers Archiv: European Journal of Physiology, 2009Co-Authors: Kamonshanok Kraidith, La-iad Nakkrasae, Nateetip Krishnamra, Walailuk Jantarajit, Jarinthorn Teerapornpuntakit, Narattaphol CharoenphandhuAbstract:Prolactin (PRL) is reported to stimulate Calcium absorption in the rat’s small intestine. However, little is known regarding its effects on the cecum, a part of the large intestine with the highest rate of intestinal Calcium Transport. We demonstrated herein by quantitative real-time polymerase chain reaction and Western blot analysis that the cecum could be a target organ of PRL since cecal epithelial cells strongly expressed PRL receptors. In Ussing chamber experiments, PRL enhanced the transcellular cecal Calcium absorption in a biphasic dose–response manner. PRL also increased the paracellular Calcium permeability and passive Calcium Transport in the cecum, which could be explained by the PRL-induced decrease in transepithelial resistance and increase in cation selectivity of the cecal epithelium. PRL actions in the cecum were abolished by inhibitors of phosphoinositide 3-kinase (PI3K), protein kinase C (PKC), and RhoA-associated coiled-coil forming kinase (ROCK), but not inhibitors of gene transcription and protein biosynthesis. In conclusion, PRL directly enhanced the transcellular and paracellular Calcium Transport in the rat cecum through the nongenomic signaling pathways involving PI3K, PKC, and ROCK.
-
chronic metabolic acidosis stimulated transcellular and solvent drag induced Calcium Transport in the duodenum of female rats
American Journal of Physiology-gastrointestinal and Liver Physiology, 2006Co-Authors: Narattaphol Charoenphandhu, Kukiat Tudpor, Naritsara Pulsook, Nateetip KrishnamraAbstract:Chronic metabolic acidosis results in a negative Calcium balance as a result of bone resorption and renal Calcium loss. However, reports on the changes in intestinal Calcium Transport have been con...
-
long term prolactin exposure differentially stimulated the transcellular and solvent drag induced Calcium Transport in the duodenum of ovariectomized rats
Experimental Biology and Medicine, 2005Co-Authors: Kukiat Tudpor, Narattaphol Charoenphandhu, Wasana Saengamnart, Nateetip KrishnamraAbstract:Prolactin, having been shown to stimulate transcellular active and solvent drag-induced Calcium Transport in the duodenum of female rats, was postulated to improve duodenal Calcium Transport in estrogen-deficient rats. The aim of the present study was, therefore, to demonstrate the effects of long-term prolactin exposure produced by anterior pituitary (AP) trans- plantation on the duodenal Calcium Transport in young (9-week- old) and adult (22-week-old) ovariectomized rats. We found that ovariectomy did not alter the transcellular active duodenal Calcium Transport in young and adult rats fed normal Calcium diet (1.0% w/w Ca) but decreased the solvent drag-induced duodenal Calcium Transport from 75.50 6 10.12 to 55.75 6 4.77 nmolhr � 1 �cm � 2 (P , 0.05) only in adult rats. Long-term prolactin exposure stimulated the transcellular active Calcium Transport in young and adult AP-grafted ovariectomized rats fed with normal Calcium diet by more than 2-fold from 7.56 6 0.79 to 16.54 6 2.05 (P , 0.001) and 9.78 6 0.72 to 15.99 6 1.75 (P , 0.001) nmolhr � 1 �cm � 2 , respectively. However, only the solvent drag- induced duodenal Calcium Transport in young rats was enhanced by prolactin from 95.51 6 10.64 to 163.20 6 18.03 nmolhr � 1 �cm � 2 (P , 0.001) whereas that in adult rats still showed a decreased flux from 75.50 6 10.12 to 47.77 6 5.42 nmolhr � 1 �cm � 2 (P , 0.05). Because oral Calcium supplement has been widely used to improve Calcium balance in estrogen- deficient animals, the effect of a high-Calcium diet (2.0% w/w Ca) was also investigated. The results showed that stimulatory action of long-term prolactin on the transcellular active duodenal Calcium Transport in both young and adult rats was diminished after being fed a high-Calcium diet. The same diet also abolished prolactin-enhanced solvent drag-induced duo- denal Calcium Transport in young and further decreased that in adult AP-grafted ovariectomized rats. We concluded that the solvent drag-induced duodenal Calcium Transport in adult rats was decreased after ovariectomy. Long-term prolactin exposure stimulated the transcellular active duodenal Calcium Transport in both young and adult rats whereas enhancing the solvent drag- induced duodenal Calcium Transport only in young rats. Effects of prolactin were abolished by a high-Calcium diet. Exp Biol Med 230:836-844, 2005.
Sylvia Christakos - One of the best experts on this subject based on the ideXlab platform.
-
evidence for a role of prolactin in Calcium homeostasis regulation of intestinal transient receptor potential vanilloid type 6 intestinal Calcium absorption and the 25 hydroxyvitamin d3 1α hydroxylase gene by prolactin
Endocrinology, 2010Co-Authors: Dare V Ajibade, Puneet Dhawan, Adam J Fechner, Mark B Meyer, Wesley J Pike, Sylvia ChristakosAbstract:Increased Calcium Transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is involved in intestinal Calcium Transport. To investigate prolactin as a hormone involved in Calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)2D3, prolactin, or prolactin + 1,25(OH)2D3. Prolactin alone (1 μg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D9k. Combined treatment with 1,25(OH)2D3 and prolactin resulted in an enhancement of the 1,25(OH)2D3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal Calcium Transport [P < 0.05 compared with 1,25(OH)2D3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)2D3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hy...
-
effect of 1 25 28 trihydroxyvitamin d2 and 1 24 25 trihydroxyvitamin d3 on intestinal calbindin d9k mrna and protein is there a correlation with intestinal Calcium Transport
Journal of Bone and Mineral Research, 2009Co-Authors: Y Z Wang, M E Bruns, Milan R Uskokovic, G A Truitt, Ronald L Horst, Timothy A Reinhardt, Sylvia ChristakosAbstract:Although analogs and metabolites of vitamin D have been tested for their calciotropic activity, very little information has been available concerning the effects of these compounds on gene expression. In this study one analog of vitamin D, 1,25,28-trihydroxyvitamin D2 [1,25,28-(OH)3D2], and one metabolite, 1,24,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3], were tested for their effect on intestinal calbindin-D9K mRNA and protein as well as for their effect on intestinal Calcium absorption and bone Calcium mobilization. These compounds were also evaluated for their ability to compete for rat intestinal 1,25-(OH)2D3 receptor sites and to induce differentiation of human leukemia (HL-60) cells as indicated by reduction of nitro blue tetrazolium. In vivo studies involved intrajugular injection of 12.5 ng 1,25-(OH)2D3 or test compound to vitamin D-deficient rats and sacrifice after 18 h. 1,25,28-Trihydroxyvitamin D2 had no effect on intestinal Calcium absorption, bone Calcium mobilization, or intestinal calbindin-D9K protein and mRNA. Competitive binding to 1,25-(OH)2D3 receptors was 0.8% of that observed using 1,25-(OH)2D3. However, 20- and 40-fold higher doses of 1,25,28-(OH)3D2 (250 and 500 ng) resulted in significant inductions in calbindin-D9K protein and mRNA (3.5 to 7.4-fold), although doses as high as 800 ng were found to have no effect on intestinal Calcium absorption or bone Calcium mobilization. 1,25,28-Trihydroxyvitamin D2, although lacking in calciotropic activity, was found to induce differentiation of HL-60 cells at high concentrations [ED50 = 15 × 10−8 M compared to ED50 = 2.5 × 10−8 M for 1,25-(OH)2D3]. 1,24,25-Trihydroxyvitamin D3 was 93% as active as 1,25-(OH)2D3 in stimulating intestinal Calcium Transport but was relatively inactive in stimulating bone Calcium mobilization. Competitive binding to the 1,25-(OH)2D3 receptor was 8% of that observed using 1,25-(OH)2D3. Although 1,24,25-(OH)3D3 was 93% as active as 1,25-(OH)2D3 in stimulating intestinal Calcium absorption, this compound was found to be 50% as active as 1,25-(OH)2D3 in stimulating calbindin-D9K protein and mRNA. The lack of a direct correlation between calbindin protein and mRNA and intestinal Calcium Transport after 1,24,25-(OH)3D3 administration or after administration of high doses of 1,25,28-(OH)3D2 suggests that factors in addition to calbindin are involved, at least in part, in vitamin D-regulated intestinal Calcium Transport.
Dare V Ajibade - One of the best experts on this subject based on the ideXlab platform.
-
evidence for a role of prolactin in Calcium homeostasis regulation of intestinal transient receptor potential vanilloid type 6 intestinal Calcium absorption and the 25 hydroxyvitamin d3 1α hydroxylase gene by prolactin
Endocrinology, 2010Co-Authors: Dare V Ajibade, Puneet Dhawan, Adam J Fechner, Mark B Meyer, Wesley J Pike, Sylvia ChristakosAbstract:Increased Calcium Transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is involved in intestinal Calcium Transport. To investigate prolactin as a hormone involved in Calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)2D3, prolactin, or prolactin + 1,25(OH)2D3. Prolactin alone (1 μg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D9k. Combined treatment with 1,25(OH)2D3 and prolactin resulted in an enhancement of the 1,25(OH)2D3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal Calcium Transport [P < 0.05 compared with 1,25(OH)2D3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)2D3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hy...
-
active intestinal Calcium Transport in the absence of transient receptor potential vanilloid type 6 and calbindin d9k
Endocrinology, 2008Co-Authors: Bryan S Benn, Euibae Jeung, Dare V Ajibade, Angela R Porta, Puneet Dhawan, Matthias A Hediger, Jibin Peng, Yi Jiang, Liesbet Lieben, Roger BouillonAbstract:To study the role of the epithelial Calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the Calcium-binding protein calbindin-D9k in intestinal Calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and TRPV6/calbindin-D9k DKO mice have serum Calcium levels similar to those of wild-type (WT) mice ( approximately 10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P 0.1, WT vs. calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-Calcium diet). Duodenal Calcium Transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO mice fed the low-Calcium diet (P < 0.05, WT vs. DKO). Active Calcium Transport was not stimulated by low dietary Calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal Calcium Transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal Calcium Transport occurs in the absence of TRPV6 and calbindin-D9k, thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin D-induced active intestinal Calcium Transport.
Liesbet Lieben - One of the best experts on this subject based on the ideXlab platform.
-
phosphate dependent luminal atp metabolism regulates transcellular Calcium Transport in intestinal epithelial cells
The FASEB Journal, 2017Co-Authors: Atsushi Uekawa, Liesbet Lieben, Hitoki Yamanaka, Yoshifumi Kimira, Mariko Uehara, Yoko Yamamoto, Shigeaki Kato, Geert Carmeliet, Ritsuko MasuyamaAbstract:Extracellular low phosphate strongly enhances intestinal Calcium absorption independently of active vitamin D [1,25(OH)2D3] signaling, but the underlying mechanisms remain poorly characterized. To elucidate the phosphate-dependent regulation of Calcium Transport, we investigated part of the enteral environment that is involved in 1,25(OH)2D3-independent Calcium absorption, which responds to dietary phosphate levels in mice that lack intestinal vitamin D receptor (Vdr) activity. Impaired Calcium absorption in intestinal Vdr-null mice was improved by dietary phosphate restriction. Accordingly, Calcium Transport in cultured intestinal epithelial cells was increased when the apical side was exposed to low phosphate levels (0.5 mM) compared with normal or high phosphate levels (1.0 or 5.0 mM, respectively). Mechanistically, low phosphate increased ATP in the apical side medium and allowed Calcium entry into epithelial cells via the P2X7 purinoreceptor, which results in increased Calcium Transport. We found tha...
-
phosphate dependent luminal atp metabolism regulates transcellular Calcium Transport in intestinal epithelial cells
The FASEB Journal, 2017Co-Authors: Atsushi Uekawa, Liesbet Lieben, Hitoki Yamanaka, Yoshifumi Kimira, Mariko Uehara, Yoko Yamamoto, Shigeaki Kato, Kosei Ito, Geert Carmeliet, Ritsuko MasuyamaAbstract:Extracellular low phosphate strongly enhances intestinal Calcium absorption independently of active vitamin D [1,25(OH)2D3] signaling, but the underlying mechanisms remain poorly characterized. To elucidate the phosphate-dependent regulation of Calcium Transport, we investigated part of the enteral environment that is involved in 1,25(OH)2D3-independent Calcium absorption, which responds to dietary phosphate levels in mice that lack intestinal vitamin D receptor ( Vdr) activity. Impaired Calcium absorption in intestinal Vdr-null mice was improved by dietary phosphate restriction. Accordingly, Calcium Transport in cultured intestinal epithelial cells was increased when the apical side was exposed to low phosphate levels (0.5 mM) compared with normal or high phosphate levels (1.0 or 5.0 mM, respectively). Mechanistically, low phosphate increased ATP in the apical side medium and allowed Calcium entry into epithelial cells via the P2X7 purinoreceptor, which results in increased Calcium Transport. We found that luminal ATP was regulated by the release and degradation of ATP at the epithelium, and phosphate restriction increased ATP release from epithelial cells via connexin-43 hemichannels. Furthermore, ATP degradation by ectonucleotide pyrophosphatase-1 was reduced, which was caused by the reduction of the MAPK cascade. These findings indicate that luminal ATP metabolism regulates transcellular Calcium Transport in the intestine by an 1,25(OH)2D3-independent mechanism in response to dietary phosphate levels.-Uekawa, A., Yamanaka, H., Lieben, L., Kimira, Y., Uehara, M., Yamamoto, Y., Kato, S., Ito, K., Carmeliet, G., Masuyama, R. Phosphate-dependent luminal ATP metabolism regulates transcellular Calcium Transport in intestinal epithelial cells.
-
active intestinal Calcium Transport in the absence of transient receptor potential vanilloid type 6 and calbindin d9k
Endocrinology, 2008Co-Authors: Bryan S Benn, Euibae Jeung, Dare V Ajibade, Angela R Porta, Puneet Dhawan, Matthias A Hediger, Jibin Peng, Yi Jiang, Liesbet Lieben, Roger BouillonAbstract:To study the role of the epithelial Calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the Calcium-binding protein calbindin-D9k in intestinal Calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and TRPV6/calbindin-D9k DKO mice have serum Calcium levels similar to those of wild-type (WT) mice ( approximately 10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P 0.1, WT vs. calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-Calcium diet). Duodenal Calcium Transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO mice fed the low-Calcium diet (P < 0.05, WT vs. DKO). Active Calcium Transport was not stimulated by low dietary Calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal Calcium Transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal Calcium Transport occurs in the absence of TRPV6 and calbindin-D9k, thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin D-induced active intestinal Calcium Transport.
