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Françoise Schoentgen - One of the best experts on this subject based on the ideXlab platform.
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Characterization of human and bovine Phosphatidylethanolamine-Binding Protein (PEBP/RKIP) interactions with morphine and morphine-glucuronides determined by noncovalent mass spectrometry.
Medical science monitor : international medical journal of experimental and clinical research, 2020Co-Authors: Cédric Atmanene, Elise Glattard, Alexis Laux, Françoise Schoentgen, Marie-hélène Metz-boutigue, Dominique Aunis, George B. Stefano, Arnaud Muller, Alain Van Dorsselaer, Sarah Sanglier-cianféraniAbstract:The Phosphatidylethanolamine-Binding Protein (PEBP/RKIP), initially found to bind Phosphatidylethanolamine (PE), has been shown to be associated with morphine derivatives. Our recent study on bovine primary chromaffin cells showed that inside secretory granules, PEBP is noncovalently associated to endogenous morphine-6-glucuronide (M6G), a highly analgesic morphine metabolite. During stress, M6G-PEBP complexes may be released into circulation to target peripheral opioid receptors. We now report the investigation of PEBP Binding properties towards morphine and morphine analogs. Noncovalent electrospray ionization mass spectrometry (ESI-MS) was used to investigate bovine and human PEBP Binding properties towards morphine and morphine-glucuronides. We describe for the first time that: (i) PEBP directly interacts with morphine glucuronides (M3G and M6G) but not with morphine, (ii) that the presence of a glucuronide group either on the 3rd or the 6th morphine's carbon does not affect these interactions, (iii) that M6G binds PEBP in a similar manner as the reference ligand PE and (iv) that PEBP displays a similar affinity for PE, M6G and M3G. Our results suggest that PEBP might protect M6G following its secretion into blood, leading to a longer half life. This study highlights the potentialities of ESI-MS to validate / invalidate the formation of Protein: ligand noncovalent complexes when low affinity binders (i.e., compounds with affinities lower than 10(3) M(-1)) are concerned.
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PEBP1/RKIP behavior: a mirror of actin-membrane organization.
Cellular and Molecular Life Sciences, 2020Co-Authors: Françoise Schoentgen, Slavica JonicAbstract:: Phosphatidylethanolamine-Binding Protein 1 (PEBP1), a small 21 kDa Protein, is implicated in several key processes of the living cell. The deregulation of PEBP1, especially its downregulation, leads to major diseases such as cancer and Alzheimer's disease. PEBP1 was found to interact with numerous Proteins, especially kinases and GTPases, generally inhibiting their activity. To understand the basic functionality of this amazing small Protein, we have considered several known processes that it modulates and we have discussed the role of each molecular target in these processes. Here, we propose that cortical actin organization, associated with membrane changes, is involved in the majority of the processes modulated by PEBP1. Furthermore, based on recent data, we summarize some key PEBP1-interacting Proteins, and we report their respective functions and focus on their relationships with actin organization. We suggest that, depending on the cell status and environment, PEBP1 is an organizer of the actin-membrane composite material.
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characterization of human and bovine Phosphatidylethanolamine Binding Protein pebp rkip interactions with morphine and morphine glucuronides determined by noncovalent mass spectrometry
Medical Science Monitor, 2009Co-Authors: Cédric Atmanene, Elise Glattard, Alexis Laux, Françoise Schoentgen, Dominique Aunis, George B. Stefano, Arnaud Muller, Alain Van Dorsselaer, Mariehelene Metzboutigue, Sarah SangliercianferaniAbstract:The Phosphatidylethanolamine-Binding Protein (PEBP/RKIP), initially found to bind Phosphatidylethanolamine (PE), has been shown to be associated with morphine derivatives. Our recent study on bovine primary chromaffi n cells showed that inside secretory granules, PEBP is noncovalently associated to endogenous morphine-6-glucuronide (M6G), a highly analgesic morphine metabolite. During stress, M6G-PEBP complexes may be released into circulation to target peripheral opioid receptors. We now report the investigation of PEBP Binding properties towards morphine and morphine analogs. http://www.medscimonit.com/fulltxt.php
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Characterization of human and bovine Phosphatidylethanolamine-Binding Protein (PEBP/RKIP) interactions with morphine and morphine-glucuronides determined by noncovalent mass spectrometry
Medical Science Monitor, 2009Co-Authors: Cédric Atmanene, Elise Glattard, Alexis Laux, Françoise Schoentgen, Marie-hélène Metz-boutigue, Alain Van Dorsselaer, George B. Stefano, Dominique Aunis, Arnaud Muller, Sarah Sanglier-cianféraniAbstract:The Phosphatidylethanolamine-Binding Protein (PEBP/RKIP), initially found to bind Phosphatidylethanolamine (PE), has been shown to be associated with morphine derivatives. Our recent study on bovine primary chromaffi n cells showed that inside secretory granules, PEBP is noncovalently associated to endogenous morphine-6-glucuronide (M6G), a highly analgesic morphine metabolite. During stress, M6G-PEBP complexes may be released into circulation to target peripheral opioid receptors. We now report the investigation of PEBP Binding properties towards morphine and morphine analogs. http://www.medscimonit.com/fulltxt.php
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the hippocampal cholinergic neurostimulating peptide the n terminal fragment of the secreted Phosphatidylethanolamine Binding Protein possesses a new biological activity on cardiac physiology
Journal of Biological Chemistry, 2004Co-Authors: Y Goumon, Françoise Schoentgen, Ingeborg Welters, Tommaso Angelone, Sylvette Chasserotgolaz, Bjorg Almas, Miriam M Fukami, Keith Langley, B Tota, Dominique AunisAbstract:Abstract Phosphatidylethanolamine-Binding Protein (PEBP), alternatively named Raf-1 kinase inhibitor Protein, is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP) corresponding to its natural N-terminal fragment, previously described to be released by hippocampal neurons. PEBP is a soluble cytoplasmic Protein, also associated with plasma and reticulum membranes of numerous cell types. In the present report, using biochemistry and cell biology techniques, we report for the first time the presence of PEBP in bovine chromaffin cell, a well described secretion model. We have examined its presence at the subcellular level and characterized this Protein on both secretory granule membranes and intragranular matrix. In addition, its presence in bovine chromaffin cell and platelet exocytotic medium, as well as in serum, was reported showing that it is secreted. Like many other Proteins that lack signal sequence, PEBP may be secreted through non-classic signal secretory mechanisms, which could be due to interactions with granule membrane lipids and lipid rafts. By two-dimensional liquid chromatography-tandem mass spectrometry, HCNP was detected among the intragranular matrix components. The observation that PEBP and HCNP were secreted with catecholamines into the circulation prompted us to investigate endocrine effects of this peptide on cardiovascular system. By using as bioassay an isolated and perfused frog (Rana esculenta) heart preparation, we show here that HCNP acts on the cardiac mechanical performance exerting a negative inotropism and counteracting the adrenergic stimulation of isoproterenol. All together, these data suggest that PEBP and HCNP might be considered as new endocrine factors involved in cardiac physiology.
Ping Zhao - One of the best experts on this subject based on the ideXlab platform.
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synthesis secretion and antifungal mechanism of a Phosphatidylethanolamine Binding Protein from the silk gland of the silkworm bombyx mori
International Journal of Biological Macromolecules, 2020Co-Authors: Yan Zhang, Muya Tang, Zhaoming Dong, Dongchao Zhao, Lingna An, Ping ZhaoAbstract:Abstract A silkworm cocoon contains several antimicrobial Proteins such as protease inhibitors and seroins to provide protection for the enclosed pupa. In this study, we identified a new Bombyx mori Phosphatidylethanolamine-Binding Protein (BmPEBP) with antimicrobial activity in the cocoon silk using semi-quantitative and quantitative RT-PCR, western blotting, and immunofluorescence. The results indicated that BmPEBP was synthesized in the middle silk gland and secreted into the sericin layer of the cocoon silk. Functional analysis showed that BmPEBP could inhibit the spore growth of four types of fungi, Candida albicans, Saccharomyces cerevisiae, Beauveria bassiana, and Aspergillus fumigates, by Binding to the fungal cell membrane. Investigation of the interaction of BmPEBP with membrane phospholipids revealed that the Protein showed a strong Binding affinity to Phosphatidylethanolamine, weak affinity to phosphatidylinositol, and no affinity to phosphatidylserine or phosphatidylcholine. Circular dichroism spectroscopy showed that Binding to Phosphatidylethanolamine caused conformational changes in the BmPEBP molecule by reducing β-sheet formation and inducing the appearance of an α-helix motif. We speculate that BmPEBP performs antifungal function in the cocoon silk through interaction with Phosphatidylethanolamine in the fungal membrane.
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functional analysis and characterization of antimicrobial Phosphatidylethanolamine Binding Protein bmpebp in the silkworm bombyx mori
Insect Biochemistry and Molecular Biology, 2019Co-Authors: Muya Tang, Yan Zhang, Zhaoming Dong, Lingna An, Xiaolu Zhang, Ping ZhaoAbstract:Abstract Phosphatidylethanolamine-Binding Proteins (PEBPs) are a class of highly conserved, biologically diverse Proteins, which are widely distributed in plants, insects, and mammals. In this study, a Bombyx mori PEBP (BmPEBP) gene was reported, which encodes a Protein composed of 209 amino acid residues. BmPEBP includes a predicted signal peptide, indicating that it is an extracellular Protein, which differs from the cytoplasmic PEBPs of plants and mammals. Recombinant soluble BmPEBP was successfully synthesized using a prokaryotic expression system and was then purified effectively by Ni2+-NTA affinity chromatography and gel filtration. Far-ultraviolet circular dichroism spectra indicated that BmPEBP had a well-defined β-sheet structure, with the β-sheet content accounting for about 41% of the Protein. BmPEBP had a relatively stable structure at temperatures ranging from 15 °C to 57.5 °C. The Tm, ΔH, and ΔS of BmPEBP were 62.27 °C ± 0.14 °C, 570.10 ± 0.17 kJ/mol, and 1.70 ± 0.03 KJ/(mol·K), respectively. Homology modeling analysis suggested that the active sites of BmPEBP were conserved, comprising Pro96, His111, and His143. Quantitative real-time PCR showed that BmPEBP was highly expressed in the silk gland and had very low expression in other tissues. However, BmPEBP expression was significantly upregulated in the larval fat body after infection with two kinds of fungi, Beauveria bassiana and Candida albicans. Moreover, in vitro fungal inhibition tests showed that BmPEBP could significantly inhibit the sporular growth of Saccharomyces cerevisiae, C. albicans, B. bassiana, and Aspergillus fumigatus. To our knowledge, this is the first report to reveal the antifungal role of a PEBP in insects.
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development and evaluation of monoclonal antibodies against Phosphatidylethanolamine Binding Protein 1 in pancreatic cancer patients
Journal of Immunological Methods, 2010Co-Authors: Xiaoting Wang, Shuangshuang Wang, Xiaojun Tang, Aixia Zhang, Tessa Grabinski, Eric A Hudson, Bree Berghuis, Craig P Webb, Ping ZhaoAbstract:Abstract Phosphatidylethanolamine Binding Protein 1 (PEBP1), also known as Raf kinase inhibitor Protein (RKIP), has been considered as a suppressor of metastasis and a prognostic marker in prostate cancer, breast cancer, gastrointestinal stromal tumors, melanoma, and epithelial ovarian cancer. In this report, recombinant PEBP1 was successfully expressed in an Escherichia coli system. A panel of monoclonal antibodies (mAbs) against PEBP1 with high specificity and affinity was generated and characterized using ELISA, western blot analysis, immunofluorescent staining and immunohistochemical staining. PEBP1 expression in normal 293 cells and a few pancreatic cancer cell lines was detected with mAb 7F12 in western blot analysis. To screen for a pair of mAbs with optimal Binding affinity to soluble PEBP1, ForteBio's Octet system was used. Sandwich ELISA with mAb pair 4F10 and 8E2 showed a linear correlation between absorbance and PEBP1 Protein concentration over a range of 7 to 100 ng/ml. MAb 4A11 detected a high level expression of PEBP1 in normal pancreatic tissue, and cancer adjacent normal pancreatic tissue in a pancreatic tissue microarray (TMA) comprising 80 human tissue cores. Pancreatic cancer tissues show a no or very weak staining intensity of PEBP1. In 69 valid cases, PEBP1 expression was significantly lower in tumor than in normal pancreas (p = 8.40E-14) and adjacent normal tissue (p = 8.46E-17). PEBP1 expression in pancreatic cancer was not associated with pTMN stage, differentiation grade and pathologic diagnosis. In conclusion, our results suggest that PEBP1 overexpresses in normal pancreas but significantly decreases its expression in pancreatic cancer tissues. Anti-PEBP1 mAbs 4A11, 4F10, 7F12, and 8E2 are potential clinical diagnostic agents for pancreatic cancer.
Iwao Ohkubo - One of the best experts on this subject based on the ideXlab platform.
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purification molecular cloning and functional characterization of swine Phosphatidylethanolamine Binding Protein 4 from seminal plasma
Biochemical and Biophysical Research Communications, 2012Co-Authors: Liping An, Peige Du, Toshinaga Maeda, Tomohisa Sakaue, Keisuke Takeuchi, Takuya Yamane, Iwao OhkuboAbstract:Abstract Phosphatidylethanolamine-Binding Proteins (PEBPs) are found in various species and have multiple functions. In this study, we purified the swine homolog of human PEBP4 (sPEBP4) from swine seminal plasma, cloned the sPEBP4 cDNA and functionally characterized this Protein. The molecular mass of the purified Protein was calculated to be 25 kDa by SDS–polyacrylamide gel electrophoresis under reducing conditions. The full-length cDNA of sPEBP4 contains 815 bp with an open reading frame of 669 bp that encodes a Protein 222 residues in length. sPEBP4 contains a putative Phosphatidylethanolamine-Binding domain between residues 79 and 195; however, this domain did not show lipid Binding activity. The overall amino acid sequence identity of PEBP4s from swine, human, mouse, bovine and canine ranges between 56.1% and 82.4%. Immunohistochemical staining and western blotting analysis showed that sPEBP4 is secreted from epithelial cells in the epididymis to the seminal plasma. To explore the role of sPEBP4 in the seminal plasma, we tested the effect of sPEBP4 on swine sperm motility. Sperms suspended in phosphate-buffered saline began to swim after the addition of purified sPEBP4, but not when swine serum albumin was added, indicating that sPEBP4 promotes sperm motility.
Jin Li - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidylethanolamine Binding Protein is not involved in µ opioid receptor mediated regulation of extracellular signal regulated kinase
Molecular Medicine Reports, 2015Co-Authors: Jiaming Bian, Ning Wu, Ruibin Su, Jin LiAbstract:Stimulation of the μ-opioid receptor activates extracellular signal-regulated kinase (ERK), however, the mechanism by which this occurs remains to be elucidated. Phosphatidylethanolamine-Binding Protein (PEBP) has been reported to act as a negative regulator of the ERK cascade (Raf-MEK-ERK) by Binding to Raf-1 kinase. In the present study, the role of PEBP in μ-opioid receptor-mediated ERK activation was investigated in Chinese hamster ovary/μ cells and SH-SY5Y cells, as well as in human embryonic kidney 293 cells expressing other types of G Protein-coupled receptors. The acute activation of μ-opioid receptors by morphine or (D-Ala2, MePhe4, Gly5-ol) enkephalin induced a rapid activation of ERK. Prolonged morphine treatment did not affect the phosphorylation level of ERK compared with control cells, but the phosphorylation level of ERK decreased markedly when cells were precipitated with naloxone following chronic morphine treatment. For the phosphorylation of PEBP, no change was identified under the designated drug treatment and exposure duration. A total of two other types of G Protein-coupled receptors, including Gs-coupled dopamine D1 receptors and Gq-coupled adrenergic α1A receptors were also investigated and only the activation of adrenergic α1A receptors induced an upregulated phosphorylation of PEBP, which was Protein kinase C activity dependent. Thus, PEBP did not have a significant role in μ-opioid receptor-mediated regulation of ERK.
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Phosphatidylethanolamine‑Binding Protein is not involved in µ‑opioid receptor-mediated regulation of extracellular signal‑regulated kinase
Molecular Medicine Reports, 2015Co-Authors: Jia‑ming Bian, Ning Wu, Rui‑bin Su, Jin LiAbstract:Stimulation of the μ-opioid receptor activates extracellular signal-regulated kinase (ERK), however, the mechanism by which this occurs remains to be elucidated. Phosphatidylethanolamine-Binding Protein (PEBP) has been reported to act as a negative regulator of the ERK cascade (Raf-MEK-ERK) by Binding to Raf-1 kinase. In the present study, the role of PEBP in μ-opioid receptor-mediated ERK activation was investigated in Chinese hamster ovary/μ cells and SH-SY5Y cells, as well as in human embryonic kidney 293 cells expressing other types of G Protein-coupled receptors. The acute activation of μ-opioid receptors by morphine or (D-Ala2, MePhe4, Gly5-ol) enkephalin induced a rapid activation of ERK. Prolonged morphine treatment did not affect the phosphorylation level of ERK compared with control cells, but the phosphorylation level of ERK decreased markedly when cells were precipitated with naloxone following chronic morphine treatment. For the phosphorylation of PEBP, no change was identified under the designated drug treatment and exposure duration. A total of two other types of G Protein-coupled receptors, including Gs-coupled dopamine D1 receptors and Gq-coupled adrenergic α1A receptors were also investigated and only the activation of adrenergic α1A receptors induced an upregulated phosphorylation of PEBP, which was Protein kinase C activity dependent. Thus, PEBP did not have a significant role in μ-opioid receptor-mediated regulation of ERK.
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roles of Phosphatidylethanolamine Binding Protein in cell signaling and its biological functions
Acta physiologica Sinica, 2013Co-Authors: Jiaming Bian, Ning Wu, Jin LiAbstract:: Phosphatidylethanolamine-Binding Protein (PEBP) is a cytoplasm soluble Protein with a high conserved structure. It has been approved recently that PEBP is a multifunctional molecule regulating several important cellular signal pathways, including ERK cascade, NF-κB pathway, and signaling of G Protein-coupled receptors. Furthermore, the role of PEBP in tumor metastasis also got a comprehensive attention in the field of clinical cancer research. Together, as a signal regulator at multiple paths in cell, PEBP is becoming a new focus in several research fields. This review is aimed to introduce the newest biological progress on PEBP.
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involvement of hippocampal Phosphatidylethanolamine Binding Protein in morphine dependence and withdrawal
Addiction Biology, 2013Co-Authors: Ning Wu, Jiaming Bian, Ying Chen, Ruibin Su, Jin LiAbstract:: Drug addiction is thought to result from an intractable and aberrant learning and memory in response to drug-related stimulation, and cholinergic neurotransmission plays an important role in this process. Phosphatidylethanolamine-Binding Protein (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP), an 11 amino acid peptide that enhances the production of choline acetyltransferase (ChAT) and assists in the development of cholinergic projections from the medial septal nuclei to the hippocampus. However, whether PEBP is involved in drug addiction remains unclear. In the present study, PEBP expression in the hippocampus, as detected by proteomics analysis, was found to be dramatically up-regulated after rats received chronic morphine treatment. Western blotting analysis revealed a specific up-regulation of PEBP expression in the hippocampus but not in any other brain regions assessed. A down-regulation of hippocampal PEBP levels induced by antisense oligodeoxynucleotides resulted in aggravated morphine dependence. Together, these findings indicate that PEBP is involved in morphine dependence. Moreover, the time course of PEBP expression changes and ChAT activity was investigated during chronic morphine treatment and withdrawal. The results showed that the hippocampal PEBP levels were up-regulated during chronic morphine treatment and returned to the baseline 3 days after withdrawal, after which PEBP levels were persistently up-regulated for 28 days after withdrawal. The changes in hippocampal ChAT activity followed a pattern that was similar to that of the PEBP levels. Taken together, these results suggest that hippocampal PEBP is involved in morphine dependence and withdrawal, perhaps through modulating cholinergic transmission in the hippocampus.
Yan Zhang - One of the best experts on this subject based on the ideXlab platform.
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synthesis secretion and antifungal mechanism of a Phosphatidylethanolamine Binding Protein from the silk gland of the silkworm bombyx mori
International Journal of Biological Macromolecules, 2020Co-Authors: Yan Zhang, Muya Tang, Zhaoming Dong, Dongchao Zhao, Lingna An, Ping ZhaoAbstract:Abstract A silkworm cocoon contains several antimicrobial Proteins such as protease inhibitors and seroins to provide protection for the enclosed pupa. In this study, we identified a new Bombyx mori Phosphatidylethanolamine-Binding Protein (BmPEBP) with antimicrobial activity in the cocoon silk using semi-quantitative and quantitative RT-PCR, western blotting, and immunofluorescence. The results indicated that BmPEBP was synthesized in the middle silk gland and secreted into the sericin layer of the cocoon silk. Functional analysis showed that BmPEBP could inhibit the spore growth of four types of fungi, Candida albicans, Saccharomyces cerevisiae, Beauveria bassiana, and Aspergillus fumigates, by Binding to the fungal cell membrane. Investigation of the interaction of BmPEBP with membrane phospholipids revealed that the Protein showed a strong Binding affinity to Phosphatidylethanolamine, weak affinity to phosphatidylinositol, and no affinity to phosphatidylserine or phosphatidylcholine. Circular dichroism spectroscopy showed that Binding to Phosphatidylethanolamine caused conformational changes in the BmPEBP molecule by reducing β-sheet formation and inducing the appearance of an α-helix motif. We speculate that BmPEBP performs antifungal function in the cocoon silk through interaction with Phosphatidylethanolamine in the fungal membrane.
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functional analysis and characterization of antimicrobial Phosphatidylethanolamine Binding Protein bmpebp in the silkworm bombyx mori
Insect Biochemistry and Molecular Biology, 2019Co-Authors: Muya Tang, Yan Zhang, Zhaoming Dong, Lingna An, Xiaolu Zhang, Ping ZhaoAbstract:Abstract Phosphatidylethanolamine-Binding Proteins (PEBPs) are a class of highly conserved, biologically diverse Proteins, which are widely distributed in plants, insects, and mammals. In this study, a Bombyx mori PEBP (BmPEBP) gene was reported, which encodes a Protein composed of 209 amino acid residues. BmPEBP includes a predicted signal peptide, indicating that it is an extracellular Protein, which differs from the cytoplasmic PEBPs of plants and mammals. Recombinant soluble BmPEBP was successfully synthesized using a prokaryotic expression system and was then purified effectively by Ni2+-NTA affinity chromatography and gel filtration. Far-ultraviolet circular dichroism spectra indicated that BmPEBP had a well-defined β-sheet structure, with the β-sheet content accounting for about 41% of the Protein. BmPEBP had a relatively stable structure at temperatures ranging from 15 °C to 57.5 °C. The Tm, ΔH, and ΔS of BmPEBP were 62.27 °C ± 0.14 °C, 570.10 ± 0.17 kJ/mol, and 1.70 ± 0.03 KJ/(mol·K), respectively. Homology modeling analysis suggested that the active sites of BmPEBP were conserved, comprising Pro96, His111, and His143. Quantitative real-time PCR showed that BmPEBP was highly expressed in the silk gland and had very low expression in other tissues. However, BmPEBP expression was significantly upregulated in the larval fat body after infection with two kinds of fungi, Beauveria bassiana and Candida albicans. Moreover, in vitro fungal inhibition tests showed that BmPEBP could significantly inhibit the sporular growth of Saccharomyces cerevisiae, C. albicans, B. bassiana, and Aspergillus fumigatus. To our knowledge, this is the first report to reveal the antifungal role of a PEBP in insects.