The Experts below are selected from a list of 25224 Experts worldwide ranked by ideXlab platform

Kazuwa Nakao - One of the best experts on this subject based on the ideXlab platform.

  • c type Natriuretic Peptide cnp guanylate cyclase b gc b system and endothelin 1 et 1 et receptor a and b system in human vasculature
    Canadian Journal of Physiology and Pharmacology, 2020
    Co-Authors: Daisuke Taura, Kazuhiro Nakao, Yasuaki Nakagawa, Hideyuki Kinoshita, Masakatsu Sone, Kazuwa Nakao
    Abstract:

    To assess the physiological and clinical implications of the C-Type Natriuretic Peptide (CNP)/guanylyl cyclase B (GC-B) system in the human vasculature, we have examined gene expressions of CNP and...

  • systemic administration of c type Natriuretic Peptide as a novel therapeutic strategy for skeletal dysplasias
    Endocrinology, 2009
    Co-Authors: Akihiro Yasoda, Toshihito Fujii, Yasato Komatsu, Hidetomo Kitamura, Eri Kondo, Naoaki Murao, Masako Miura, Naotetsu Kanamoto, Hiroshi Arai, Kazuwa Nakao
    Abstract:

    Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-Type Natriuretic Peptide (CNP), a member of the Natriuretic Peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.

  • cyclic gmp dependent protein kinase ii plays a critical role in c type Natriuretic Peptide mediated endochondral ossification
    Endocrinology, 2002
    Co-Authors: Takashi Miyazawa, Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yasato Komatsu, Alexander Pfeifer, Yoshihiro Ogawa, Franz Hofmann, Kazuwa Nakao
    Abstract:

    Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-Type Natriuretic Peptide (CNP), a third member of the Natriuretic Peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2 / mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2 / mice differ from CNP-deficient mice (Nppc / mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2 / mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2 / mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification. (Endocrinology 143: 3604 –3610, 2002)

  • Natriuretic Peptide regulation of endochondral ossification evidence for possible roles of the c type Natriuretic Peptide guanylyl cyclase b pathway
    Journal of Biological Chemistry, 1998
    Co-Authors: Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yoshihiro Ogawa, Michio Suda, Kiyoshi Tanaka, Kiyoshi Mori, Yoko Sakuma, Kohei Shiota, Kazuwa Nakao
    Abstract:

    Abstract The Natriuretic Peptide family consists of three structurally related endogenous ligands: atrial Natriuretic Peptide (ANP), brain Natriuretic Peptide (BNP), and C-Type Natriuretic Peptide (CNP). The biological actions of Natriuretic Peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The Natriuretic Peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-Peptide GC-coupled Natriuretic Peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

  • c type Natriuretic Peptide as an autocrine paracrine regulator of osteoblast evidence for possible presence of bone Natriuretic Peptide system
    Biochemical and Biophysical Research Communications, 1996
    Co-Authors: Michio Suda, Akihiro Yasoda, Yasato Komatsu, Yoshihiro Ogawa, Kiyoshi Tanaka, Mitsuo Fukushima, Koshi Natsui, Hiroshi Itoh, Kazuwa Nakao
    Abstract:

    Abstract C-Type Natriuretic Peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial Natriuretic Peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [ 3 H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of “bone Natriuretic Peptide system.”

Yoshihiro Ogawa - One of the best experts on this subject based on the ideXlab platform.

  • cyclic gmp dependent protein kinase ii plays a critical role in c type Natriuretic Peptide mediated endochondral ossification
    Endocrinology, 2002
    Co-Authors: Takashi Miyazawa, Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yasato Komatsu, Alexander Pfeifer, Yoshihiro Ogawa, Franz Hofmann, Kazuwa Nakao
    Abstract:

    Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-Type Natriuretic Peptide (CNP), a third member of the Natriuretic Peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2 / mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2 / mice differ from CNP-deficient mice (Nppc / mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2 / mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2 / mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification. (Endocrinology 143: 3604 –3610, 2002)

  • oxidative stress augments secretion of endothelium derived relaxing Peptides c type Natriuretic Peptide and adrenomedullin
    Journal of Hypertension, 2000
    Co-Authors: Tae Hwa Chun, Yoshihiro Ogawa, Hiroshi Itoh, Takatoshi Saito, K Yamahara, Kentaro Doi, Yuko Mori, Jun K Yamashita, Tokuji Tanaka, Mayumi Inoue
    Abstract:

    Objective Excess oxidative stress is one of the major metabolic abnormalities on vascular walls in hypertension and atherosclerosis. In order to further elucidate the endothelial function under oxidative stress, the effect of hydrogen peroxide (H 2 O 2 ) on expression of two novel endothelium-derived vasorelaxing Peptides, C-Type Natriuretic Peptide (CNP) and adrenomedullin (AM) from bovine carotid artery endothelial cells (BCAECs) was examined. Methods BCAECs were treated with H 2 O 2 (0.1-1.0 mmol/ I) and/or an antioxidant, N-acetylcysteine (NAC) (5-10 mmol/l), and incubated for 48 h. The concentrations of CNP and AM were measured with the specific radioimmun assays that we originally developed. CNP and AM mRNA expressions were also examined by reverse transcription-polymerase chain reaction (RT-PCR). Results Treatment of BCAECs with 0.5 and 1 mmol/l H 2 O 2 induced 9-and 10-fold increases of CNP concentration in the media. Addition of 10 mmol/l NAC significantly suppressed the effect of H 2 O 2 by 52%. RT-PCR analysis showed that CNP mRNA expression in BCAECs was also rapidly augmented within 1 h with H 2 O 2 (1 mmol/l) treatment, and reached a peak at 3 h to show a 10-fold increase. AM secretion from BCAECs also increased to two-fold with exposure to 0.5 mmol/l H 2 O 2 , accompanied with the augmented level of AM mRNA. NAC 10 mmol/l completely suppressed the effect of H 2 O 2 on AM secretion. Conclusions In this study, it has been demonstrated that H 2 O 2 augments endothelial secretion of the two endothelium-derived relaxing Peptides, CNP and AM. Our findings suggest the increased secretion of CNP and AM from endothelium under oxidative stress may function to compensate the impaired nitric oxide-dependent vasorelaxation in hypertension and atherosclerosis.

  • Natriuretic Peptide regulation of endochondral ossification evidence for possible roles of the c type Natriuretic Peptide guanylyl cyclase b pathway
    Journal of Biological Chemistry, 1998
    Co-Authors: Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yoshihiro Ogawa, Michio Suda, Kiyoshi Tanaka, Kiyoshi Mori, Yoko Sakuma, Kohei Shiota, Kazuwa Nakao
    Abstract:

    Abstract The Natriuretic Peptide family consists of three structurally related endogenous ligands: atrial Natriuretic Peptide (ANP), brain Natriuretic Peptide (BNP), and C-Type Natriuretic Peptide (CNP). The biological actions of Natriuretic Peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The Natriuretic Peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-Peptide GC-coupled Natriuretic Peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

  • shear stress augments expression of c type Natriuretic Peptide and adrenomedullin
    Hypertension, 1997
    Co-Authors: Tae Hwa Chun, Naohisa Tamura, Yoshihiro Ogawa, Hiroshi Itoh, Kentaro Doi, Jun K Yamashita, Mayumi Inoue, Kazuhiko Takaya, Toshio Igaki, Ken Masatsugu
    Abstract:

    Abstract Shear stress is known to dilate blood vessels and exert antiproliferative effects on vascular walls; these effects have been ascribed to shear stress–induced upregulation of endothelium-derived vasoactive substances, mainly nitric oxide and prostacyclin. We have demonstrated the significance of C-Type Natriuretic Peptide (CNP) as a novel endothelium-derived relaxing Peptide (EDRP) that shares a cGMP pathway with nitric oxide. Adrenomedullin is a recently isolated EDRP that elevates intracellular cAMP as prostacyclin does. To elucidate the possible role of these EDRPs under shear stress, we examined the effect of physiological shear stress on CNP mRNA expression in endothelial cells derived from the human umbilical vein (HUVECs), bovine aorta (BAECs), and murine lymph nodes (MLECs) as well as adrenomedullin mRNA expression in HUVECs. CNP mRNA was stimulated prominently in HUVECs under shear stress of 15 dyne/cm 2 in a time-dependent manner (4 hours, sixfold increase compared with that in the static condition; 24 hours, 30-fold increase). Similar results were obtained in BAECs (4 hours, twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that was dependent on shear stress intensity was also observed (5 dyne/cm 2 , 2.5-fold increase of static; 15 dyne/cm 2 , 4.5-fold increase). Increased CNP secretion was also confirmed by the specific radioimmunoassay for CNP. Adrenomedullin mRNA expression in HUVECs increased under shear stress of 15 dyne/cm 2 in a time-dependent manner (4 hours, 1.2-fold increase of static; 24 hours, threefold increase) and shear stress intensity–dependent manner (15 dyne/cm 2 , threefold increase compared with that at 5 dyne/cm 2 ). These results suggest that the coordinated augmentation of mRNA expression of these novel EDRPs may constitute shear stress–dependent vasodilator and antiproliferative effects.

  • c type Natriuretic Peptide as an autocrine paracrine regulator of osteoblast evidence for possible presence of bone Natriuretic Peptide system
    Biochemical and Biophysical Research Communications, 1996
    Co-Authors: Michio Suda, Akihiro Yasoda, Yasato Komatsu, Yoshihiro Ogawa, Kiyoshi Tanaka, Mitsuo Fukushima, Koshi Natsui, Hiroshi Itoh, Kazuwa Nakao
    Abstract:

    Abstract C-Type Natriuretic Peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial Natriuretic Peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [ 3 H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of “bone Natriuretic Peptide system.”

Akihiro Yasoda - One of the best experts on this subject based on the ideXlab platform.

  • intracerebroventricular administration of c type Natriuretic Peptide suppresses food intake via activation of the melanocortin system in mice
    Diabetes, 2013
    Co-Authors: Nobuko Yamadagoto, Goro Katsuura, Ken Ebihara, Megumi Inuzuka, Yukari Ochi, Toru Kusakabe, Noriko Satohasahara, Akihiro Yasoda, Yui Yamashita, Hiroyuki Ariyasu
    Abstract:

    C-Type Natriuretic Peptide (CNP) and its receptor are abundantly distributed in the brain, especially in the arcuate nucleus (ARC) of the hypothalamus associated with regulating energy homeostasis. To elucidate the possible involvement of CNP in energy regulation, we examined the effects of intracerebroventricular administration of CNP on food intake in mice. The intracerebroventricular administration of CNP-22 and CNP-53 significantly suppressed food intake on 4-h refeeding after 48-h fasting. Next, intracerebroventricular administration of CNP-22 and CNP-53 significantly decreased nocturnal food intake. The increment of food intake induced by neuroPeptide Y and ghrelin was markedly suppressed by intracerebroventricular administration of CNP-22 and CNP-53. When SHU9119, an antagonist for melanocortin-3 and melanocortin-4 receptors, was coadministered with CNP-53, the suppressive effect of CNP-53 on refeeding after 48-h fasting was significantly attenuated by SHU9119. Immunohistochemical analysis revealed that intracerebroventricular administration of CNP-53 markedly increased the number of c-Fos–positive cells in the ARC, paraventricular nucleus, dorsomedial hypothalamus, ventromedial hypothalamic nucleus, and lateral hypothalamus. In particular, c-Fos–positive cells in the ARC after intracerebroventricular administration of CNP-53 were coexpressed with α-melanocyte–stimulating hormone immunoreactivity. These results indicated that intracerebroventricular administration of CNP induces an anorexigenic action, in part, via activation of the melanocortin system.

  • systemic administration of c type Natriuretic Peptide as a novel therapeutic strategy for skeletal dysplasias
    Endocrinology, 2009
    Co-Authors: Akihiro Yasoda, Toshihito Fujii, Yasato Komatsu, Hidetomo Kitamura, Eri Kondo, Naoaki Murao, Masako Miura, Naotetsu Kanamoto, Hiroshi Arai, Kazuwa Nakao
    Abstract:

    Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-Type Natriuretic Peptide (CNP), a member of the Natriuretic Peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.

  • cyclic gmp dependent protein kinase ii plays a critical role in c type Natriuretic Peptide mediated endochondral ossification
    Endocrinology, 2002
    Co-Authors: Takashi Miyazawa, Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yasato Komatsu, Alexander Pfeifer, Yoshihiro Ogawa, Franz Hofmann, Kazuwa Nakao
    Abstract:

    Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-Type Natriuretic Peptide (CNP), a third member of the Natriuretic Peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2 / mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2 / mice differ from CNP-deficient mice (Nppc / mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2 / mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2 / mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification. (Endocrinology 143: 3604 –3610, 2002)

  • Natriuretic Peptide regulation of endochondral ossification evidence for possible roles of the c type Natriuretic Peptide guanylyl cyclase b pathway
    Journal of Biological Chemistry, 1998
    Co-Authors: Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yoshihiro Ogawa, Michio Suda, Kiyoshi Tanaka, Kiyoshi Mori, Yoko Sakuma, Kohei Shiota, Kazuwa Nakao
    Abstract:

    Abstract The Natriuretic Peptide family consists of three structurally related endogenous ligands: atrial Natriuretic Peptide (ANP), brain Natriuretic Peptide (BNP), and C-Type Natriuretic Peptide (CNP). The biological actions of Natriuretic Peptides are thought to be mediated through the activation of two guanylyl cyclase (GC)-coupled receptor subtypes (GC-A and GC-B). In this study, we examined the effects of ANP and CNP, which are endogenous ligands for GC-A and GC-B, respectively, on bone growth using an organ culture of fetal mouse tibias, an in vitro model of endochondral ossification. CNP increased the cGMP production much more potently than ANP, thereby resulting in an increase in the total longitudinal bone length. Histological examination revealed an increase in the height of the proliferative and hypertrophic chondrocyte zones in fetal mouse tibias treated with CNP. The Natriuretic Peptide stimulation of bone growth, which was mimicked by 8-bromo-cGMP, was inhibited by HS-142-1, a non-Peptide GC-coupled Natriuretic Peptide receptor antagonist. The spontaneous increase in the total longitudinal bone growth and cGMP production was also inhibited significantly by HS-142-1. CNP mRNA was expressed abundantly in fetal mouse tibias, where no significant amounts of ANP and BNP mRNAs were detected. A considerable amount of GC-B mRNA was present in fetal mouse tibias. This study suggests the physiologic significance of the CNP/GC-B pathway in the process of endochondral ossification.

  • c type Natriuretic Peptide as an autocrine paracrine regulator of osteoblast evidence for possible presence of bone Natriuretic Peptide system
    Biochemical and Biophysical Research Communications, 1996
    Co-Authors: Michio Suda, Akihiro Yasoda, Yasato Komatsu, Yoshihiro Ogawa, Kiyoshi Tanaka, Mitsuo Fukushima, Koshi Natsui, Hiroshi Itoh, Kazuwa Nakao
    Abstract:

    Abstract C-Type Natriuretic Peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial Natriuretic Peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [ 3 H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of “bone Natriuretic Peptide system.”

Yasato Komatsu - One of the best experts on this subject based on the ideXlab platform.

  • systemic administration of c type Natriuretic Peptide as a novel therapeutic strategy for skeletal dysplasias
    Endocrinology, 2009
    Co-Authors: Akihiro Yasoda, Toshihito Fujii, Yasato Komatsu, Hidetomo Kitamura, Eri Kondo, Naoaki Murao, Masako Miura, Naotetsu Kanamoto, Hiroshi Arai, Kazuwa Nakao
    Abstract:

    Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-Type Natriuretic Peptide (CNP), a member of the Natriuretic Peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.

  • cyclic gmp dependent protein kinase ii plays a critical role in c type Natriuretic Peptide mediated endochondral ossification
    Endocrinology, 2002
    Co-Authors: Takashi Miyazawa, Akihiro Yasoda, Naohisa Tamura, Hideki Chusho, Yasato Komatsu, Alexander Pfeifer, Yoshihiro Ogawa, Franz Hofmann, Kazuwa Nakao
    Abstract:

    Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-Type Natriuretic Peptide (CNP), a third member of the Natriuretic Peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2 / mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2 / mice differ from CNP-deficient mice (Nppc / mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2 / mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2 / mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification. (Endocrinology 143: 3604 –3610, 2002)

  • c type Natriuretic Peptide as an autocrine paracrine regulator of osteoblast evidence for possible presence of bone Natriuretic Peptide system
    Biochemical and Biophysical Research Communications, 1996
    Co-Authors: Michio Suda, Akihiro Yasoda, Yasato Komatsu, Yoshihiro Ogawa, Kiyoshi Tanaka, Mitsuo Fukushima, Koshi Natsui, Hiroshi Itoh, Kazuwa Nakao
    Abstract:

    Abstract C-Type Natriuretic Peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial Natriuretic Peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [ 3 H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of “bone Natriuretic Peptide system.”

  • cytokine induced c type Natriuretic Peptide cnp secretion from vascular endothelial cells evidence for cnp as a novel autocrine paracrine regulator from endothelial cells
    Endocrinology, 1993
    Co-Authors: Shin Ichi Suga, Yasato Komatsu, Yoshihiro Ogawa, Hiroshi Itoh, Norio Hama, Takaaki Yoshimasa, Kazuwa Nakao
    Abstract:

    We previously demonstrated that C-Type Natriuretic Peptide (CNP), originally isolated from the porcine brain, is produced by endothelial cells and proposed that CNP can exert local control over vascular tone and growth as a local regulator from endothelial cells. Since cytokines play pivotal roles in the control of vascular tone and structure, we have examined effects of various cytokines on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP. While interleukin (IL)-2 had no significant effect on CNP secretion, IL-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha stimulated CNP secretion in a time- and dose-dependent manner. Among them, TNF-alpha, one of the key mediators for inflammation and vascular remodeling, induced more than two orders of magnitude increase in CNP secretion. In addition, lipopolysaccharide (LPS) potently stimulated CNP secretion. These results indicate that IL-1, TNF-alpha and LPS, the endotoxin itself, can regulate local vascular tone and growth ...

Yoshio Takei - One of the best experts on this subject based on the ideXlab platform.

  • Sequence, circulating levels, and expression of C-Type Natriuretic Peptide in a euryhaline elasmobranch, Carcharhinus leucas.
    General and comparative endocrinology, 2005
    Co-Authors: W. Gary Anderson, Susumu Hyodo, Takehiro Tsukada, Lara Meischke, Richard D. Pillans, Jonathan P. Good, Yoshio Takei, Gordon Cramb, Craig E. Franklin, Neil Hazon
    Abstract:

    The present study has examined expression and circulating levels of C-Type Natriuretic Peptide (CNP) in the euryhaline bull shark, Carcharhinus leucas. Complementary DNA and deduced amino acid sequence for CNP in C leucas were determined by RACE methods. Homology of CNP amino acid sequence in C. leucas was high both for proCNP and for mature CNP when compared with previously identified elasmobranch CNPs. Mature CNP sequence in C. leucas was identical to that in Triakis seyllia and Seyliorhinus canicula. Levels of expression of CNP mRNA were significantly decreased in the atrium but did not change in either the brain or ventricle following acclimation to a SW environment. However, circulating levels of CNP significantly increased from 86.0 +/- 7.9 fmol ml(-1) in FW to 144.9 +/- 19.5 fmol ml(-1) in SW. The results presented demonstrate that changes in environmental salinity influences both synthesis of CNP from the heart and also circulating levels in C. leucas. Potential stimulus for release and modes of action are discussed. (c) 2005 Elsevier Inc. All rights reserved.

  • Characterisation of C-Type Natriuretic Peptide receptors in the gill of dogfish Triakis scyllia
    The Journal of endocrinology, 1998
    Co-Authors: H Sakaguchi, Yoshio Takei
    Abstract:

    Only C-Type Natriuretic Peptide (CNP) has been identified in primitive elasmobranch fish. CNP is the most conserved molecule in the Natriuretic Peptide family, suggesting that it is the ancestral type. As a first step to investigating the ancestral type of Natriuretic Peptide receptors, CNP receptors were characterised in an elasmobranch (dogfish, Triakis scyllia) by radioligandbinding analysis using 125 I-[Tyr 0 ]-dogfish (df )CNP. None of the modifications of the CNP molecule that occur at the time of iodination (addition of a Tyr residue at the N-terminus, introduction of iodine into Tyr 0 or oxidation of Met 17 )a Vect the aYnity of dfCNP for the receptors. Neither did oxidation of Met 17 decrease the ability of CNP to stimulate cGMP production. In the tissues examined, CNP receptors were densest in the gill cells followed by the intestine, interrenal gland and rectal gland, all of which are involved in osmoregulation in elasmobranchs. CNP-stimulated guanylate cyclase (GC) activity was highest in the interrenal gland, intestine, brain and rectal gland, followed by the gill cells. Since the gill cells seem to contain both GC-coupled and uncoupled receptors, this tissue was used to characterise dogfish CNP receptors. Scatchard analysis of the saturation isotherm revealed two classes of binding site: one has a Kd of 24·0 pm and B max of 59·9 fmol/mg protein, and the other has low aYnity (K d >1nm) and high capacity (B max >200 fmol/mg protein). The higher-aYnity binding sites may represent GC-uncoupled receptors, because C-ANF, a specific ligand for GC-uncoupled receptors, almost completely displaced CNP binding. AYnitylabelling experiments showed that dogfish receptors have molecular masses of about 90, 170 and 340 kDa, and CNP binding to the former two receptors is inhibited by C-ANF. After reduction with 2-mercaptoethanol, most 170 kDa labelling was shifted to 90 kDa. It is concluded that GC-uncoupled receptors in the dogfish gill have higher molecular mass than those of mammals and eel (about 65 kDa), and are present mostly as monomers even in non-reducing conditions. However, a small population of GC-coupled receptors is also present, as demonstrated by an increase in cGMP production.

  • Isolation of high-molecular-weight C-Type Natriuretic Peptide from the heart of a cartilaginous fish (European dogfish, Scyliorhinus canicula).
    FEBS letters, 1991
    Co-Authors: Reiko Suzuki, Akiyoshi Takahashi, Yoshio Takei
    Abstract:

    A high-molecular-weight form of C-Type Natriuretic Peptide (CNP) was isolated from both cardiac atria and ventrieles of European dogfish, Scyliorhinus canicula, and its primary structure was determined. The Peptide consists of 115 amino acid residues, in which the C-terminal 22 residues show high homology to CNPs identified to date. This is the first direct evidence for the presence of Natriuretic Peptide in the cartilaginous fish, and for the presence of CNP in an organ other than the brain.