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[PMID]:28114332
[Au] Autor:Cong L; Cheng Y; Cawley NX; Murthy SR; Loh YP
[Ad] Endereço:Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
[Ti] Título:A Novel Single Nucleotide T980C Polymorphism in the Human Carboxypeptidase E Gene Results in Loss of Neuroprotective Function.
[So] Source:PLoS One;12(1):e0170169, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Report of a human with a homozygous truncating null mutation of the Carboxypeptidase E (CPE) gene with endocrinological and neurological deficits prompted us to search for other mutations in the human CPE gene that might be linked to disease. We searched an EST database and identified from a small population of patients, a novel T to C single nucleotide polymorphism (SNP) in the CPE gene at bp980 of exon 4, herein called TC-CPE. This introduces a tryptophan to arginine (W235R) mutation in the catalytic domain of human CPE protein. Over-expression of TC-CPE in N2A cells, a neuroendocrine cell line, showed that it was synthesized, but was found in lesser amounts compared to over-expressed WT-CPE in these cells. Furthermore, TC-CPE was secreted poorly from these N2A cells. The levels of TC-CPE were significantly increased after the N2A cells were treated with MG132 (a proteasome inhibitor), suggesting that TC-CPE was targeted to proteasomes for degradation in N2A cells. In addition, TC-CPE induced ER stress as demonstrated by the increased expression of CHOP in N2A cells. Double labeling of CPE and calnexin (and ER marker) suggested the accumulation of TC-CPE in the ER, and the accumulation appears to be enhanced by the treatment of MG132 in the cells. Moreover, the secreted levels of TC-CPE were not affected by the treatment of MG132 in the cells. Over-expression studies revealed that while N2A cells transfected with WT-CPE showed reduced cytotoxicity when challenged with H2O2 compared to cells expressing an empty vector, cells transfected with TC-CPE had no effect. Furthermore, WT-CPE condition medium showed protective effect against oxidative stress, but not TC-CPE condition medium. Although co-expression of WT-CPE and TC-CPE in N2A cells resulted in the reduction in secretion of WT-CPE, co-expression of WT-CPE and TC-CPE did not significantly affect the protective effect of WT-CPE. Taken together, we have identified a novel SNP in the CPE gene which results in the loss of its neuroprotective function in cells and may confer neurological disorders in humans.
[Mh] Termos MeSH primário: Carboxipeptidase H/genética
Sistema Nervoso/patologia
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Linhagem Celular
Seres Humanos
Fases de Leitura Aberta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0170169


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[PMID]:27788574
[Au] Autor:Mizutani A; Inoko H; Tanaka M
[Ad] Endereço:Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan.
[Ti] Título:Carboxypeptidase E, Identified As a Direct Interactor of Growth Hormone, Is Important for Efficient Secretion of the Hormone.
[So] Source:Mol Cells;39(10):756-761, 2016 Oct.
[Is] ISSN:0219-1032
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:We have identified 88 interactor candidates for human growth hormone (GH) by the yeast two-hybrid assay. Among those, we focused our efforts on carboxypeptidase E (CPE), which has been thought to play a key role in sorting prohormones, such as pro-opiomelanocortin (POMC), to regulated secretory vesicles. We found that CPE co-localizes with and interacts with GH in AtT20 pituitary cells. Downregulation of CPE led to decreased levels of GH secretion, consistent with involvement of CPE in GH sorting/secretion. Our binding assay with bacterially expressed proteins suggested that GH directly interacts with CPE but in a manner different from POMC.
[Mh] Termos MeSH primário: Carboxipeptidase H/metabolismo
Hormônio do Crescimento Humano/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico
Carboxipeptidase H/genética
Hormônio do Crescimento Humano/secreção
Seres Humanos
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
12629-01-5 (Human Growth Hormone); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170426
[Lr] Data última revisão:
170426
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161030
[St] Status:MEDLINE


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[PMID]:27783296
[Au] Autor:Kruchinina AD; Gamzin SS; Tengin MT
[Ad] Endereço:Department of General Biology and Biochemistry, Penza State University, Penza, Russia. a.d.kruchinina@mail.ru.
[Ti] Título:Effects of Single Administration of Bupropion on Carboxypeptidase E Activity in Structures of Rat Brain.
[So] Source:Bull Exp Biol Med;161(6):788-791, 2016 Oct.
[Is] ISSN:1573-8221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Depression is associated with changes in the levels of some neurotransmitters in various brain structures. Being the key enzyme of peptide processing, carboxypeptidase E regulates their levels in various structures of the nervous system. Single injection of bupropion induced long-lasting changes in carboxypeptidase E activity in all brain structures. The decrease in enzyme activity observed in 12 and 24 h after bupropion injection confirmed the inhibiting effect of the drug on the hypothalamic-pituitary-adrenal axis. Activation of the enzyme in the medulla oblongata, hypothalamus, and hippocampus observed in 72 h after bupropion administration probably leads to enhanced synthesis and secretion of regulatory peptides (reduced during stress and depression) and stimulation of neurogenesis. Changes in enzyme activity can be a mechanism regulating the level of bioactive peptides involved in the pathogenesis of depression.
[Mh] Termos MeSH primário: Antidepressivos de Segunda Geração/farmacologia
Bupropiona/farmacologia
Carboxipeptidase H/antagonistas & inibidores
Sistema Hipotálamo-Hipofisário/efeitos dos fármacos
Sistema Hipófise-Suprarrenal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Animais não Endogâmicos
Carboxipeptidase H/metabolismo
Esquema de Medicação
Hipocampo/efeitos dos fármacos
Hipocampo/fisiologia
Sistema Hipotálamo-Hipofisário/fisiologia
Hipotálamo/efeitos dos fármacos
Hipotálamo/fisiologia
Injeções Intraperitoneais
Bulbo/efeitos dos fármacos
Bulbo/fisiologia
Hipófise/efeitos dos fármacos
Hipófise/fisiologia
Sistema Hipófise-Suprarrenal/fisiologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents, Second-Generation); 01ZG3TPX31 (Bupropion); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170209
[Lr] Data última revisão:
170209
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE


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[PMID]:27375026
[Au] Autor:Skalka N; Caspi M; Lahav-Ariel L; Loh YP; Hirschberg K; Rosin-Arbesfeld R
[Ad] Endereço:Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
[Ti] Título:Carboxypeptidase E (CPE) inhibits the secretion and activity of Wnt3a.
[So] Source:Oncogene;35(50):6416-6428, 2016 Dec 15.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The Wnt pathway has essential roles in cell proliferation, cell fate determination and tumorigenesis by regulating the expression of a wide range of target genes. As a core signaling cascade, the canonical Wnt pathway is regulated at different levels by numerous proteins. We have previously shown that carboxypeptidase E (CPE) is a novel regulator of the canonical Wnt signaling pathway. Here, we show that CPE and the Wnt3a ligand are co-secreted from cells. We show that although the C'-terminal Lys residue of Wnt3a is critical for its activity and is important for the effect of CPE on the Wnt pathway, CPE does not execute its effect by removing this Wnt3a residue. Interestingly, CPE through its N'-terminal sequence, forms aggregates with Wnt3a and possible endoplasmic reticulum (ER) stress leading to its loss of function. Together, our current results provide a mechanistic insight into the way CPE regulates the canonical Wnt signaling pathway.
[Mh] Termos MeSH primário: Carboxipeptidase H/fisiologia
Proteína Wnt3A/metabolismo
[Mh] Termos MeSH secundário: Animais
Células COS
Cercopithecus aethiops
Estresse do Retículo Endoplasmático
Células HEK293
Seres Humanos
Agregados Proteicos
Via de Sinalização Wnt
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Aggregates); 0 (Wnt3A Protein); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160705
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2016.173


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[PMID]:26803519
[Au] Autor:Huang SF; Wu HD; Chen YT; Murthy SR; Chiu YT; Chang Y; Chang IC; Yang X; Loh YP
[Ad] Endereço:Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhuna, Miaoli, 350, Taiwan. sfhuang@nhri.org.tw.
[Ti] Título:Carboxypeptidase E is a prediction marker for tumor recurrence in early-stage hepatocellular carcinoma.
[So] Source:Tumour Biol;37(7):9745-53, 2016 Jul.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor recurrence and metastasis are the major causes of death for hepatocellular carcinoma (HCC) patients who are able to receive curative resection. Identifying the predicting biomarkers for tumor recurrence would improve their survival. RNA extracted from fresh frozen tumors and adjacent non-tumor liver tissues of 120 HCC patients were obtained from Taiwan Liver Cancer Network (TLCN) in year 2010 for determination of the carboxypeptidase E (CPE) expression level (including its splicing mutant CPE-ΔN) in the tumor tissue (T) and paired non-tumor liver tissue (N) by real-time quantitative polymerase chain reaction. All patients were male, had chronic hepatitis B virus infection, were in the early pathology stage, and received curative resection. The T/N ratio of the CPE expression level was correlated with the updated survival data from TLCN in 2015. The CPE expression level in the 120 HCC patients was divided into three groups according to the T/N ratio: <1, ≥1 and ≤2, and >2, respectively. By multivariate analyses, the recurrence-free survival (RFS) was only significantly associated with the pathology stage and the CPE expression level. For overall survival (OS), only the CPE expression level was the significant prognostic factor. The CPE expression level was also significantly correlated with the tumor recurrence for both stage I (p = 0.0106) and stage II patients (p = 0.0006). The CPE mRNA expression level in HCC can be a useful biomarker for predicting tumor recurrence in HCC patients who are in the early pathology stage and able to receive curative resection.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Carboxipeptidase H/genética
Carcinoma Hepatocelular/patologia
Neoplasias Hepáticas/patologia
Fígado/metabolismo
Recidiva Local de Neoplasia/diagnóstico
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/enzimologia
Carcinoma Hepatocelular/cirurgia
Seguimentos
Seres Humanos
Fígado/patologia
Neoplasias Hepáticas/enzimologia
Neoplasias Hepáticas/cirurgia
Masculino
Meia-Idade
Invasividade Neoplásica
Recidiva Local de Neoplasia/enzimologia
Recidiva Local de Neoplasia/cirurgia
Estadiamento de Neoplasias
Prognóstico
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (RNA, Messenger); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160125
[St] Status:MEDLINE
[do] DOI:10.1007/s13277-016-4814-7


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[PMID]:26760117
[Au] Autor:Ishii J; Yazawa T; Chiba T; Shishido-Hara Y; Arimasu Y; Sato H; Kamma H
[Ad] Endereço:Department of Pathology (J.I., T.C., Y.A., H.K.), Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan; Department of Diagnostic Pathology (T.Y.), Chiba University Graduate School of Medicine, Chiba 260-8670, Japan; Department of Anatomic Pathology (Y.S.-H.), Tokyo Medical University,
[Ti] Título:PROX1 Promotes Secretory Granule Formation in Medullary Thyroid Cancer Cells.
[So] Source:Endocrinology;157(3):1289-98, 2016 Mar.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mechanisms of endocrine secretory granule (SG) formation in thyroid C cells and medullary thyroid cancer (MTC) cells have not been fully elucidated. Here we directly demonstrated that PROX1, a developmental homeobox gene, is transcriptionally involved in SG formation in MTC, which is derived from C cells. Analyses using gene expression databases on web sites revealed that, among thyroid cancer cells, MTC cells specifically and highly express PROX1 as well as several SG-forming molecule genes. Immunohistochemical analyses showed that in vivo MTC and C cells expressed PROX1, although follicular thyroid cancer and papillary thyroid cancer cells, normal follicular cells did not. Knockdown of PROX1 in an MTC cells reduced SGs detected by electron microscopy, and decreased expression of SG-related genes (chromogranin A, chromogranin B, secretogranin II, secretogranin III, synaptophysin, and carboxypeptidase E). Conversely, the introduction of a PROX1 transgene into a papillary thyroid cancer and anaplastic thyroid cancer cells induced the expression of SG-related genes. Reporter assays using the promoter sequence of chromogranin A showed that PROX1 activates the chromogranin A gene in addition to the known regulatory mechanisms, which are mediated via the cAMP response element binding protein and the repressor element 1-silencing transcription factor. Furthermore, chromatin immunoprecipitation-PCR assays demonstrated that PROX1 binds to the transcriptional regulatory element of the chromogranin A gene. In conclusion, PROX1 is an important regulator of endocrine SG formation in MTC cells.
[Mh] Termos MeSH primário: Adenocarcinoma Folicular/genética
Adenoma/genética
Carcinoma Neuroendócrino/genética
Carcinoma/genética
Regulação Neoplásica da Expressão Gênica/genética
Proteínas de Homeodomínio/genética
Vesículas Secretórias/genética
Neoplasias da Glândula Tireoide/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Adenocarcinoma Folicular/metabolismo
Adenoma/metabolismo
Adulto
Idoso
Idoso de 80 Anos ou mais
Carboxipeptidase H/genética
Carcinoma/metabolismo
Carcinoma Neuroendócrino/metabolismo
Carcinoma Papilar
Imunoprecipitação da Cromatina
Cromogranina A/genética
Cromogranina B/genética
Cromograninas/genética
Feminino
Técnicas de Introdução de Genes
Técnicas de Silenciamento de Genes
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Secretogranina II/genética
Sinaptofisina/genética
Glândula Tireoide/metabolismo
Neoplasias da Glândula Tireoide/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromogranin A); 0 (Chromogranin B); 0 (Chromogranins); 0 (Homeodomain Proteins); 0 (SCG2 protein, human); 0 (SCG3 protein, human); 0 (SYP protein, human); 0 (Secretogranin II); 0 (Synaptophysin); 0 (Tumor Suppressor Proteins); 0 (prospero-related homeobox 1 protein); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160114
[St] Status:MEDLINE
[do] DOI:10.1210/en.2015-1973


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[PMID]:26695643
[Au] Autor:Shen HW; Tan JF; Shang JH; Hou MZ; Liu J; He L; Yao SZ; He SY
[Ad] Endereço:Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, No.58, Zhongshan 2 Road, Guangzhou, 510080, People's Republic of China.
[Ti] Título:CPE overexpression is correlated with pelvic lymph node metastasis and poor prognosis in patients with early-stage cervical cancer.
[So] Source:Arch Gynecol Obstet;294(2):333-42, 2016 Aug.
[Is] ISSN:1432-0711
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Elevated carboxypeptidase E (CPE) levels play crucial roles in tumorigenesis and metastasis. This study investigated the expression and clinicopathological significance of CPE in early-stage cervical cancer. METHODS: Elevated carboxypeptidase E expression was analyzed using quantitative polymerase chain reaction and western blotting in normal cervical tissue, cervical cancer cell lines, and in cervical cancer tissues and adjacent noncancerous tissues (ANTs) from the same patient. Immunohistochemistry (IHC) was used to examine CPE expression in tissue samples from 112 patients with early-stage cervical cancer (FIGO stages Ia2-IIa2), 60 patients with cervical intraepithelial neoplasia, and 19 patients with normal cervical tissues (NCTs). Associations between CPE expression and prognostic and diagnostic factors were evaluated statistically. RESULTS: CPE expression was significantly higher in cervical cancer cell lines and tissues than in normal tissues and ANTs. Semi-quantitative analysis of IHC indicated that CPE gradually increased from CIN I to cervical cancer, but was absent in NCTs. CPE expression was seen in 40.2 % (45/112) of the cervical cancer samples. CPE expression was significantly associated with FIGO stage (P = 0.003), tumor size (P = 0.012), stromal invasion (P < 0.001), lymphovascular space invasion (P = 0.016), parametrial infiltration (P = 0.027), vaginal involvement (P = 0.007), postoperative adjuvant therapy (P = 0.024), recurrence (P < 0.001), survival (P < 0.001), and pelvic lymph node metastasis (PLNM) (P < 0.001), and it was significantly higher in tissues from patients with PLNM than without PLNM. Logistic regression analysis identified high-level CPE expression as an independent risk factor for PLNM (P = 0.001). Patients with higher CPE expression had shorter overall survival duration than patients with lower CPE expression. Univariate and multivariate Cox-regression analyses suggested that high-level CPE expression is an independent prognostic factor for overall survival in early-stage cervical cancer. CONCLUSIONS: High-level CPE expression was associated with a poor prognosis in early-stage cervical cancer. CPE may serve as a biomarker for predicting PLNM and survival in these patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Carboxipeptidase H/metabolismo
Neoplasia Intraepitelial Cervical/metabolismo
Metástase Linfática/genética
Pelve/patologia
Neoplasias do Colo do Útero/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Biomarcadores Tumorais/análise
Biomarcadores Tumorais/genética
Western Blotting
Carboxipeptidase H/genética
Neoplasia Intraepitelial Cervical/mortalidade
Neoplasia Intraepitelial Cervical/patologia
China/epidemiologia
Feminino
Seres Humanos
Imuno-Histoquímica
Linfonodos/patologia
Metástase Linfática/patologia
Meia-Idade
Recidiva Local de Neoplasia/patologia
Estadiamento de Neoplasias
Reação em Cadeia da Polimerase
Prognóstico
Neoplasias do Colo do Útero/metabolismo
Neoplasias do Colo do Útero/mortalidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151224
[St] Status:MEDLINE
[do] DOI:10.1007/s00404-015-3985-6


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[PMID]:26646096
[Au] Autor:Cawley NX; Rathod T; Young S; Lou H; Birch N; Loh YP
[Ad] Endereço:Section on Cellular Neurobiology (N.X.C., T.R., S.Y., H.L., Y.P.L.), Program in Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4480; and School of Biological Sciences (N.B.), Centre
[Ti] Título:Carboxypeptidase E and Secretogranin III Coordinately Facilitate Efficient Sorting of Proopiomelanocortin to the Regulated Secretory Pathway in AtT20 Cells.
[So] Source:Mol Endocrinol;30(1):37-47, 2016 Jan.
[Is] ISSN:1944-9917
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Proopiomelanocortin (POMC) is a multivalent prohormone that can be processed into at least 7 biologically active peptide hormones. Processing can begin in the trans-Golgi network (TGN) and continues in the secretory granules of the regulated secretory pathway (RSP). Sorting of POMC into these granules is a complex process. Previously, a membrane-associated form of carboxypeptidase E (CPE) was shown to bind to POMC and facilitate its trafficking into these granules. More recently, secretogranin III (SgIII) was also found to affect POMC trafficking. Here, we show by RNA silencing that CPE and SgIII play a synergistic role in the trafficking of POMC to granules of the RSP in AtT20 cells. Reduction of either protein resulted in increased constitutive secretion of POMC and chromogranin A, which was increased even further when both proteins were reduced together, indicative of missorting at the TGN. In SgIII-reduced cells, POMC accumulated in a compartment that cofractionated and colocalized with syntaxin 6, a marker of the TGN, on sucrose density gradients and in immunocytochemistry, respectively, indicating an accumulation of this protein in the presumed sorting compartment. Regulated secretion of ACTH, as a measure of sorting and processing of POMC in mature granules, was reduced in the SgIII down-regulated cells but was increased in the CPE down-regulated cells. These results suggest that multiple sorting systems exist, providing redundancy to ensure the important task of continuous and accurate trafficking of prohormones to the granules of the RSP for the production of peptide hormones.
[Mh] Termos MeSH primário: Carboxipeptidase H/metabolismo
Cromograninas/metabolismo
Corticotrofos/metabolismo
Pró-Opiomelanocortina/metabolismo
Via Secretória/fisiologia
Vesículas Secretórias/metabolismo
[Mh] Termos MeSH secundário: Animais
Carboxipeptidase H/genética
Linhagem Celular
Cromograninas/genética
Camundongos
Transporte Proteico/fisiologia
Interferência de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromogranins); 0 (secretogranin III); 66796-54-1 (Pro-Opiomelanocortin); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170101
[Lr] Data última revisão:
170101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151210
[St] Status:MEDLINE
[do] DOI:10.1210/me.2015-1166


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[PMID]:26539877
[Au] Autor:Kruchinina AD; Gengin MT
[Ad] Endereço:Penza State University, Penza, Russia.
[Ti] Título:[Effect of reboxetine on activity of carboxypeptidase E in the nerve tissue of rats].
[So] Source:Biomed Khim;61(5):657-60, 2015 Sep-Oct.
[Is] ISSN:2310-6972
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Depression is one of the most common mental disorders, but its etiology is not completely understood. It is assumed that peptidergic system components are involved in the formation of this pathology. Neuropeptides play an important role in the regulation of mental and emotional states. Сarboxypeptidase E is a key enzyme of peptide processing; it regulates neuropeptide levels in the various structures of the nervous system. We have studied effects of a single dose of reboxetine on the activity of carboxypeptidase E in various brain regions and the adrenal glands of rats. The reboxetine injection decreased carboxypeptidase E activity in the pituitary gland (12 h after injection), in the pituitary gland, the quadrigeminal bodies, the medulla oblongata, the hypothalamus, the hippocampus and the amygdala (24 h after injection), in the pituitary gland and striatum (72 h after injection). The enzyme activity in adrenal glands remained basically unchanged. Apparently, the decrease of carboxypeptidase E activity may influence the level of regulatory peptides involved in the pathogenesis of depression.
[Mh] Termos MeSH primário: Antidepressivos/farmacologia
Carboxipeptidase H/antagonistas & inibidores
Morfolinas/farmacologia
[Mh] Termos MeSH secundário: Glândulas Suprarrenais/efeitos dos fármacos
Glândulas Suprarrenais/enzimologia
Tonsila do Cerebelo/efeitos dos fármacos
Tonsila do Cerebelo/enzimologia
Animais
Animais não Endogâmicos
Carboxipeptidase H/metabolismo
Corpo Estriado/efeitos dos fármacos
Corpo Estriado/enzimologia
Hipocampo/efeitos dos fármacos
Hipocampo/enzimologia
Hipotálamo/efeitos dos fármacos
Hipotálamo/enzimologia
Masculino
Bulbo/efeitos dos fármacos
Bulbo/enzimologia
Hipófise/efeitos dos fármacos
Hipófise/enzimologia
Ratos
Teto do Mesencéfalo/efeitos dos fármacos
Teto do Mesencéfalo/enzimologia
[Pt] Tipo de publicação:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antidepressive Agents); 0 (Morpholines); 947S0YZ36I (reboxetine); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:151106
[Lr] Data última revisão:
151106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151106
[St] Status:MEDLINE
[do] DOI:10.18097/PBMC20156105657


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[PMID]:26406335
[Au] Autor:Stanfill A; Hathaway D; Cashion A; Homayouni R; Cowan P; Thompson C; Madahian B; Conley Y
[Ad] Endereço:Health Promotion and Development, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
[Ti] Título:A Pilot Study of Demographic and Dopaminergic Genetic Contributions to Weight Change in Kidney Transplant Recipients.
[So] Source:PLoS One;10(9):e0138885, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Kidney transplant recipients often experience a significant amount of weight gain in the first year post-transplantation. While demographic factors such as age, race, and sex have been associated with weight gain in this population, these factors do not explain all of the variability seen. A number of studies have suggested that genetics also plays a critical role in weight changes. Recently, alterations in the activity of the neurotransmitter dopamine have been associated with weight change, and gene expression studies in kidney transplant recipients have supported this association. The purpose of this pilot study is to first examine the feasibility and methodology, and then to examine the associations of age, race, sex, and genotype for 13 SNPs and 3 VNTRs in 9 dopaminergic pathway genes (ANKK1, DRD2, DRD3, DRD4, SLC6A3/DAT1, MAOA, MAOB, COMT, CPE) for associations with percent weight change at 12 months post-transplantation. Seventy kidney transplant recipients had demographic and clinical data collected as a part of a larger observational study. DNA was extracted from repository buffy coat samples taken at the time of transplant, and genotyped using Taqman and PCR based methods. Three SNPs were independently associated with percent weight change: ANKK1 rs1800497 (r = -0.28, p = 0.05), SLC6A3/DAT1 rs6347 (p = 0.046), and CPE rs1946816 (p = 0.028). Stepwise regression modelling confirmed the combined associations of age (p = 0.0021), DRD4 VNTR 4/5 genotype (p = 0.0074), and SLC6A3/DAT1 rs6347 CC genotype (p = 0.0009) and TT genotype (p = 0.0004) with percent weight change in a smaller sample (n = 35) of these kidney transplant recipients that had complete genotyping. These associations indicate that there may be a genetic, and an age component to weight changes post transplantation.
[Mh] Termos MeSH primário: Carboxipeptidase H/genética
Proteínas da Membrana Plasmática de Transporte de Dopamina/genética
Proteínas Serina-Treonina Quinases/genética
Receptores de Dopamina D4/genética
Transplantados
Ganho de Peso/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Estudos de Associação Genética
Predisposição Genética para Doença
Seres Humanos
Transplante de Rim
Masculino
Meia-Idade
Repetições Minissatélites
Projetos Piloto
Polimorfismo de Nucleotídeo Único
Fatores de Risco
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (DRD4 protein, human); 0 (Dopamine Plasma Membrane Transport Proteins); 0 (SLC6A3 protein, human); 137750-34-6 (Receptors, Dopamine D4); EC 2.7.11.1 (ANKK1 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases); EC 3.4.17.10 (Carboxypeptidase H)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170408
[Lr] Data última revisão:
170408
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0138885



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