The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
Sabina Janciauskiene - One of the best experts on this subject based on the ideXlab platform.
-
Acute phase Protein α1-antitrypsin - A novel regulator of Angiopoietin-like Protein 4 transcription and secretion in human cells
European Respiratory Journal, 2014Co-Authors: Eileen Frenzel, Sabine Wrenger, Stephan Immenschuh, Rembert Koszulla, Ravi Mahadeva, Joachim Deeg, Mario A. Marcondes, Sabina JanciauskieneAbstract:Angiopoietin-like Protein 4 (angptl4, peroxisome proliferator-activated receptor (PPAR) gamma induced Angiopoietin-Related Protein) is a multifunctional Protein associated with acute phase response. The regulation of angptl4 expression are largely unknown. This study is the first to show that human α1-antitrypsin (A1AT) up-regulates expression and release of angplt4 in human blood mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2 to 174-fold, relative to controls. In endothelial cells the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml of A1AT (11-fold induction versus controls). In ten emphysema patients with A1AT therapy (Prolastin) plasma angptl4 levels were higher relative to patients without therapy [ng/ml, mean (95% confidence interval) 127.1 (99.5-154.6) versus 76.8 (54.8-98.8), respectively, p=0.045] and corRelated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pre-treated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of hypoxia inducible factor 1-α, an up-regulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute phase Protein A1AT is a physiological regulator of angptl4, another acute phase Protein.
-
Acute-Phase Protein α1-Antitrypsin—A Novel Regulator of Angiopoietin-like Protein 4 Transcription and Secretion
Journal of immunology (Baltimore Md. : 1950), 2014Co-Authors: Eileen Frenzel, Sabine Wrenger, Stephan Immenschuh, Ravi Mahadeva, Rembert Koczulla, H. Joachim Deeg, Charles A. Dinarello, Tobias Welte, A. Mario Marcondes, Sabina JanciauskieneAbstract:The Angiopoietin-like Protein 4 (angptl4, also known as peroxisome proliferator–activated receptor [PPAR]γ–induced Angiopoietin-Related Protein) is a multifunctional Protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5–154.6] versus 76.8 [54.8–98.8], respectively, p = 0.045) and corRelated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase Protein A1AT is a physiological regulator of angptl4, another acute-phase Protein.
William J. Larochelle - One of the best experts on this subject based on the ideXlab platform.
-
Angioarrestin: a unique Angiopoietin-Related Protein with anti-angiogenic properties.
Biochemical and biophysical research communications, 2005Co-Authors: Mohanraj Dhanabal, Michael Jeffers, William J. Larochelle, Henri LichensteinAbstract:The process of angiogenesis plays a pivotal role in embryogenesis, wound healing, and tumorigenesis through the growth of new blood vessels from pre-existing vasculature. Among the angiogenic factors recently identified as specific for vascular endothelium are the Angiopoietins. In depth characterization of the Angiopoietins has allowed investigators to better understand the molecular basis of blood vessel formation and vascular endothelial cell function. In this review, we describe Angiopoietins and Related family members, with particular emphasis on a recently identified Protein known as angioarrestin. Our investigations clearly demonstrate that angioarrestin is an anti-angiogenic molecule. The effects of angioarrestin on tumor cell progression and specific aspects of the angiogenic cascade in in vitro models are further discussed.
-
CR064, a fully human monoclonal antibody to Angiopoietin Related Protein 4 (ARP4) inhibits ARP4-mediated angiogenesis and renal cell carcinoma survival in vitro
Cancer Research, 2005Co-Authors: Haihong Zhong, Henri Lichenstein, Ferenc L. Boldog, Seth Ettenberg, Mohan Dhanabal, Melanie Baron, Nikolai V. Khramtsov, Qing Zhou, Gulshan Ara, William J. LarochelleAbstract:3006 Angiopoietin Related Proteins (ARPs) play a pivotal role in vascular formation and homeostasis. ARP4, a secreted Protein, retains the characteristic Angiopoietin family N-terminal coiled-coil domain and C-terminal fibrinogen-like domain. RTQ PCR analysis revealed transcript expression predominantly in adipose and liver tissues. Strikingly, ARP4 mRNA expression is also elevated in clear cell renal carcinoma as compared to adjacent non-tumor tissue suggesting a role in the neovascularization and progression of this disease. Our results confirm and extend the proposed role of ARP4 in the angiogenesis and progression of renal carcinoma. In this study, we report the biological characterization of purified recombinant ARP4 and that it acts both as a proangiogenic factor for endothelial cells and as a survival factor for 786-0 renal carcinoma cells. Based on these observations, we hypothesized that a monoclonal antibody raised against ARP4 might inhibit ARP4-induced activities and be useful in the treatment of renal carcinoma. Therefore, fully human ARP4 monoclonal antibodies (CR064) were generated using XenoMax technology. Selection criteria for CR064 mAbs included potent affinity, binding specificity and the ability to inhibit ARP4-mediated HUVEC migration as well as 786-0 cell survival. At a concentration of 250ng/ml, ARP4 caused approximately 2-fold enhancement of HUVEC migration and induced tube formation in matrigel. The effects of ARP4 on HUVEC migration were inhibited by CR064 in a dose dependent manner with an IC50 of 7nM. The enhancement of tube formation was also blocked at an IC50 of 27 nM. Coincidently, ARP4 (500ng/ml) caused an increase in the survival of 786-0 cells which was inhibited by CR064 monoclonal antibodies in a dose dependent manner (IC50 of 27nM). Taken together, these data suggest that CR064, a fully human monoclonal antibody against ARP4, plays a dual role in that it inhibits both ARP4-mediated angiogenesis and survival of renal carcinoma cells in vitro . These observations support further investigation of CR064 fully human monoclonal antibodies that neutralize ARP4 activities for the treatment of renal cell carcinoma.
-
Angioarrestin: an antiangiogenic Protein with tumor-inhibiting properties.
Cancer research, 2002Co-Authors: Mohanraj Dhanabal, Michael Jeffers, William J. Larochelle, John L. Herrmann, Luca Rastelli, William F. Mcdonald, Rajeev A. Chillakuru, Meijia Yang, Ferenc L. Boldog, Muralidhara PadigaruAbstract:The Angiopoietins comprise a family of Proteins that have pro or antiangiogenic activities. Through a proprietary technology designed to identify transcripts of all expressed genes, we isolated a cDNA encoding an Angiopoietin-Related Protein that we designate angioarrestin. The mRNA expression profile of angioarrestin was striking in that it was downregulated in many tumor tissues when compared with adjacent nontumor tissue, suggesting a role for this Protein in tumor inhibition. To test this hypothesis, we ectopically expressed angioarrestin in HT1080 tumor cells and measured pulmonary tumor nodule formation in nude mice. HT1080 cells expressing angioarrestin showed a marked reduction in the number and size of tumor nodules. In vitro, the recombinant Protein was systematically tested in a number of endothelial cell assays and found to block critical processes involved in the angiogenic cascade, such as vascular endothelial growth factor/basic fibroblast growth factor-mediated endothelial cell proliferation, migration, tubular network formation, and adhesion to extracellular matrix Proteins. These findings reveal a novel function for angioarrestin as an angiogenesis inhibitor and indicate that the molecule may be a potential cancer therapeutic.
Jun-dae Kim - One of the best experts on this subject based on the ideXlab platform.
-
Cloning of cDNA for a novel fibrinogen/Angiopoietin-Related Protein, FARP.
Molecules and cells, 2001Co-Authors: Jyung Hyun Lee, Ji Min Seo, Myung-kon Kim, Jun-dae KimAbstract:Using a low abundant gene screening strategy in the human dermal papilla cell cDNA library, we isolated a novel cDNA, which was 1,872 bp of nucleotides in length and contained an open reading frame encoding 405 amino acids. We designated it 'fibrinogen/Angiopoietin-Related Protein' (FARP) as it contained the characteristic coiled-coil domain and fibrinogen-like domain in the NH2- and COOH-terminal, which are conserved in Angiopoietins. FARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence. Recently, a very similar gene, HFARP, was cloned and they have a difference of only 18 amino acids in N-terminus. While HFARP was expressed only in the liver, northern blot analysis showed that FARP mRNA is abundantly expressed in the liver, placenta, prostate, and ovary in human adult tissues. It was also expressed in the fetal liver and lung carcinoma cell line. Further study will be needed to clarify the function of the FARP gene.
-
cloning of cdna for a novel fibrinogen Angiopoietin Related Protein farp
Molecules and Cells, 2001Co-Authors: Jyung Hyun Lee, Ji Min Seo, Myung-kon Kim, Jun-dae KimAbstract:Using a low abundant gene screening strategy in the human dermal papilla cell cDNA library, we isolated a novel cDNA, which was 1,872 bp of nucleotides in length and contained an open reading frame encoding 405 amino acids. We designated it 'fibrinogen/Angiopoietin-Related Protein' (FARP) as it contained the characteristic coiled-coil domain and fibrinogen-like domain in the NH2- and COOH-terminal, which are conserved in Angiopoietins. FARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence. Recently, a very similar gene, HFARP, was cloned and they have a difference of only 18 amino acids in N-terminus. While HFARP was expressed only in the liver, northern blot analysis showed that FARP mRNA is abundantly expressed in the liver, placenta, prostate, and ovary in human adult tissues. It was also expressed in the fetal liver and lung carcinoma cell line. Further study will be needed to clarify the function of the FARP gene.
Eileen Frenzel - One of the best experts on this subject based on the ideXlab platform.
-
Acute phase Protein α1-antitrypsin - A novel regulator of Angiopoietin-like Protein 4 transcription and secretion in human cells
European Respiratory Journal, 2014Co-Authors: Eileen Frenzel, Sabine Wrenger, Stephan Immenschuh, Rembert Koszulla, Ravi Mahadeva, Joachim Deeg, Mario A. Marcondes, Sabina JanciauskieneAbstract:Angiopoietin-like Protein 4 (angptl4, peroxisome proliferator-activated receptor (PPAR) gamma induced Angiopoietin-Related Protein) is a multifunctional Protein associated with acute phase response. The regulation of angptl4 expression are largely unknown. This study is the first to show that human α1-antitrypsin (A1AT) up-regulates expression and release of angplt4 in human blood mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2 to 174-fold, relative to controls. In endothelial cells the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml of A1AT (11-fold induction versus controls). In ten emphysema patients with A1AT therapy (Prolastin) plasma angptl4 levels were higher relative to patients without therapy [ng/ml, mean (95% confidence interval) 127.1 (99.5-154.6) versus 76.8 (54.8-98.8), respectively, p=0.045] and corRelated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pre-treated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of hypoxia inducible factor 1-α, an up-regulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute phase Protein A1AT is a physiological regulator of angptl4, another acute phase Protein.
-
Acute-Phase Protein α1-Antitrypsin—A Novel Regulator of Angiopoietin-like Protein 4 Transcription and Secretion
Journal of immunology (Baltimore Md. : 1950), 2014Co-Authors: Eileen Frenzel, Sabine Wrenger, Stephan Immenschuh, Ravi Mahadeva, Rembert Koczulla, H. Joachim Deeg, Charles A. Dinarello, Tobias Welte, A. Mario Marcondes, Sabina JanciauskieneAbstract:The Angiopoietin-like Protein 4 (angptl4, also known as peroxisome proliferator–activated receptor [PPAR]γ–induced Angiopoietin-Related Protein) is a multifunctional Protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5–154.6] versus 76.8 [54.8–98.8], respectively, p = 0.045) and corRelated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase Protein A1AT is a physiological regulator of angptl4, another acute-phase Protein.
Jyung Hyun Lee - One of the best experts on this subject based on the ideXlab platform.
-
Cloning of cDNA for a novel fibrinogen/Angiopoietin-Related Protein, FARP.
Molecules and cells, 2001Co-Authors: Jyung Hyun Lee, Ji Min Seo, Myung-kon Kim, Jun-dae KimAbstract:Using a low abundant gene screening strategy in the human dermal papilla cell cDNA library, we isolated a novel cDNA, which was 1,872 bp of nucleotides in length and contained an open reading frame encoding 405 amino acids. We designated it 'fibrinogen/Angiopoietin-Related Protein' (FARP) as it contained the characteristic coiled-coil domain and fibrinogen-like domain in the NH2- and COOH-terminal, which are conserved in Angiopoietins. FARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence. Recently, a very similar gene, HFARP, was cloned and they have a difference of only 18 amino acids in N-terminus. While HFARP was expressed only in the liver, northern blot analysis showed that FARP mRNA is abundantly expressed in the liver, placenta, prostate, and ovary in human adult tissues. It was also expressed in the fetal liver and lung carcinoma cell line. Further study will be needed to clarify the function of the FARP gene.
-
cloning of cdna for a novel fibrinogen Angiopoietin Related Protein farp
Molecules and Cells, 2001Co-Authors: Jyung Hyun Lee, Ji Min Seo, Myung-kon Kim, Jun-dae KimAbstract:Using a low abundant gene screening strategy in the human dermal papilla cell cDNA library, we isolated a novel cDNA, which was 1,872 bp of nucleotides in length and contained an open reading frame encoding 405 amino acids. We designated it 'fibrinogen/Angiopoietin-Related Protein' (FARP) as it contained the characteristic coiled-coil domain and fibrinogen-like domain in the NH2- and COOH-terminal, which are conserved in Angiopoietins. FARP has a highly hydrophobic region at the N-terminus that is typical of a secretory signal sequence. Recently, a very similar gene, HFARP, was cloned and they have a difference of only 18 amino acids in N-terminus. While HFARP was expressed only in the liver, northern blot analysis showed that FARP mRNA is abundantly expressed in the liver, placenta, prostate, and ovary in human adult tissues. It was also expressed in the fetal liver and lung carcinoma cell line. Further study will be needed to clarify the function of the FARP gene.