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[PMID]:29315320
[Au] Autor:Chao WC; Tseng CH; Chien YC; Sheu CC; Tsai MJ; Fang WF; Chen YM; Kao KC; Hu HC; Perng WC; Yang KY; Chen WC; Liang SJ; Wu CL; Wang HC; Chan MC; TSIRC (Taiwan Severe Influenza Research Consortium)
[Ad] Endereço:Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
[Ti] Título:Association of day 4 cumulative fluid balance with mortality in critically ill patients with influenza: A multicenter retrospective cohort study in Taiwan.
[So] Source:PLoS One;13(1):e0190952, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fluid balance is a fundamental management of patients with sepsis, and this study aimed to investigate the impact of cumulative fluid balance on critically ill patients with influenza admitted to an intensive care unit (ICU). METHODS: This multicenter retrospective cohort study was conducted by the Taiwan Severe Influenza Research Consortium (TSIRC) which includes eight medical centers. Patients with virology-proven influenza infection admitted to ICUs between October 2015 and March 2016 were included for analysis. RESULTS: A total of 296 patients were enrolled (mean age: 61.4±15.6 years; 62.8% men), and 92.2% (273/296) of them required mechanical ventilation. In the survivors, the daily fluid balance was positive from day 1 to day 3, and then gradually became negative from day 4 to day 7, whereas daily fluid balance was continuously positive in the non-survivors. Using the cumulative fluid balance from day 1-4 as a cut-off point, we found that a negative cumulative day 1-4 fluid balance was associated with a lower 30-day mortality rate (log-rank test, P = 0.003). To evaluate the impact of shock on this association, we divided the patients into shock and non-shock groups. The positive correlation between negative day 1-4 fluid balance and mortality was significant in the non-shock group (log-rank test, P = 0.008), but not in the shock group (log-rank test, P = 0.396). In a multivariate Cox proportional hazard regression model adjusted for age, sex, cerebrovascular disease, and PaO2/FiO2, day 1-4 fluid balance was independently associated with a higher 30-day mortality rate (aHR 1.088, 95% CI: 1.007-1.174). CONCLUSIONS: A negative day 1-4 cumulative fluid balance was associated with a lower mortality rate in critically ill patients with influenza. Our findings indicate the critical role of conservative fluid strategy in the management of patients with complicated influenza.
[Mh] Termos MeSH primário: Estado Terminal
Influenza Humana/mortalidade
Equilíbrio Hidroeletrolítico
[Mh] Termos MeSH secundário: Idoso
Feminino
Seres Humanos
Influenza Humana/fisiopatologia
Unidades de Terapia Intensiva
Masculino
Meia-Idade
Estudos Retrospectivos
Taiwan/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190952


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[PMID]:29251884
[Au] Autor:Georgiades D
[Ti] Título:A BALANCING ACT: MAINTAINING ACCURATE FLUID BALANCE CHARTING.
[So] Source:Aust Nurs Midwifery J;24(6):28-31, 2016 12.
[Is] ISSN:2202-7114
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Fluid balance charting is not a new practice based issue in nursing (Chung et al. 2002; Jeyapala et al. 2015). Evidence reveals that fluid balance charts have been poorly and inaccurately maintained since 1985 (Chung et al, 2002; Scales & Pilsworth, 2008).
[Mh] Termos MeSH primário: Registros de Enfermagem
Equilíbrio Hidroeletrolítico/fisiologia
[Mh] Termos MeSH secundário: Eficiência Organizacional
Hidratação
Seres Humanos
Recursos Humanos de Enfermagem no Hospital
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:N
[Da] Data de entrada para processamento:171219
[St] Status:MEDLINE


  3 / 24065 MEDLINE  
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[PMID]:29244466
[Au] Autor:Timofeeva MR; Lukina SA
[Ti] Título:Surfactant system and water balance of the lungs in modeling of neurodegeneration and focus of pathological activity in the substantia nigra.
[So] Source:Patol Fiziol Eksp Ter;60(3):31-5, 2016 Jul-Sep.
[Is] ISSN:0031-2991
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:The comparative analysis of surfactant metabolism and water balance of the lungs in modeling the formation and neurodegeneration focus of pathological activity in the substantia nigra of the brain. Methods: Experiments were performed on male rats - nonlinear, including the control, sham operated with unilateral stereotaxic administration of the neurotoxin 6-hydroxydopamine (Sigma) in the substantia nigra compact part and the implantation of cobalt metal nanopowder (Berlin) in the reticular part of the structure. Complex investigations included determination of surfactant phospholipid fractions by thin layer chromatography, total phospholipids and cholesterol in the bronchoalveolar lavage and surface-active properties by the Wilhelmy method, phospholipase activity, lipid peroxidation intensity on the content of TBA-active products in the lung tissue, evaluation of water balance using the gravimetric method. Results: It has been established that the introduction of intranigral neurotoxin and implantation of cobalt in the structure of the brain called the deterioration of the surface activity of the alveolar lining set against the backdrop of an imbalance of fractional composition of surfactant lipids with multidirectional changes in the amount of phospholipids and the degree of hydration of the lung. Induction focus of pathological activity in the substantia nigra was accompanied by an increase in alveolar phospholipids by lysophosphatidylcholine, sphingomyelin, phosphatidylethanolamine, intensification of lipid peroxidation of the lung tissue and organ hyperhydration. Modeling neurodegeneration - reduction of total phospholipids, phosphatidylcholine and lysophosphatidylcholine accumulation in terms of activation of phospholipase hydrolysis, increasing blood supply to the lungs. Conclusion: Metabolism of surfactant lipids and water balance in the lung, along with changes of rhythmogenesis and mode of ventilation, may lead to the development of disregulation of pneumopathy with dysfunction of the substantia nigra of the brain.
[Mh] Termos MeSH primário: Pulmão/metabolismo
Doenças Neurodegenerativas/metabolismo
Surfactantes Pulmonares/metabolismo
Substância Negra/metabolismo
Equilíbrio Hidroeletrolítico
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Pulmão/patologia
Masculino
Doenças Neurodegenerativas/patologia
Ratos
Substância Negra/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pulmonary Surfactants)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  4 / 24065 MEDLINE  
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[PMID]:29244457
[Au] Autor:Urakova MA; Bryndina IG
[Ti] Título:Water balance of lung and nitrogen oxide in blood at experimental autoimmune encephalomyelitis after capsaicin blockade of vagus nerve.
[So] Source:Patol Fiziol Eksp Ter;60(3):18-22, 2016 Jul-Sep.
[Is] ISSN:0031-2991
[Cp] País de publicação:Russia (Federation)
[La] Idioma:eng
[Ab] Resumo:The purpose of the research: To study the water balance of lung and NO level in blood in experimental autoimmune encephalomyelitis combined with capsaicin blockade of vagus nerve. Methods: Experiments were conducted on 47 adult (16-week-old) male rats weighing 220-280 g. To simulate the experimental autoimmune encephalomyelitis (EAE) rats were subcutaneously injected with encephalitogenic mixture in complete Freund's adjuvant (0.2 ml; the content of inactivated Mycobacterium tuberculosis was 5 mg/ml) at the rate of 100 mg of homologous spinal cord homogenate per animal. Сapsaicin blockade was performed by bilateral application of 50 uM capsaicin («Sigma¼) on the neck portions of vagus nerves. The animals were divided into 4 groups: intact rats - control group1; rats with EAE; rats with capsaicin application on vagus nerve + EAE; sham operated rats subjected to vagus nerves allocation without the subsequent capsaicin application + EAE - control group 2. The next parameters were detected: the content of nitric oxide in blood plasma; protein content in broncho-alveolar lavage fluid; lung water balance indices including the amount of total, extra- and intravascular fluid and blood supply of lungs, which were calculated based on wet and dry lung mass and the hemoglobin content in blood and lung tissue determined by hemiglobincyanide method. Results: It was found that EAE is accompanied by an increase of total fluid, extravascular fluid (EVF) and blood supply of lungs on the background of increasing content of nitric oxide in arterial (art) and venous (ven) blood. In EAE and its combination with bilateral capsaicin blockade of vagus nerve a strong negative correlation between the NOart / NOven coefficient and EVF amount was found out. The blockade of capsaicin-sensitive vagal afferents normalized lung water balance impaired in EAE and restored the levels of nitric oxide in blood plasma. Conclusion: The obtained results suggest that capsaicin-sensitive vagal afferents with NO-ergic mechanisms involvment take part in the development of pulmonary hyperhydration during experimental autoimmune encephalomyelitis.
[Mh] Termos MeSH primário: Capsaicina/efeitos adversos
Encefalomielite Autoimune Experimental
Pulmão
Óxidos de Nitrogênio
Nervo Vago
Equilíbrio Hidroeletrolítico
[Mh] Termos MeSH secundário: Animais
Capsaicina/farmacologia
Encefalomielite Autoimune Experimental/sangue
Encefalomielite Autoimune Experimental/imunologia
Pulmão/imunologia
Pulmão/metabolismo
Masculino
Óxidos de Nitrogênio/sangue
Óxidos de Nitrogênio/imunologia
Ratos
Equilíbrio Hidroeletrolítico/efeitos dos fármacos
Equilíbrio Hidroeletrolítico/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Nitrogen Oxides); S07O44R1ZM (Capsaicin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


  5 / 24065 MEDLINE  
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[PMID]:29283518
[Au] Autor:Ivanova VV; Milto IV; Sukhodolo IV; Serebryakova ON; Buzenkova AV
[Ti] Título:Digestive and Nondigestive Functions of Rodents' Salivary Glands.
[So] Source:Usp Fiziol Nauk;48(1):66-79, 2017 Jan-Mar.
[Is] ISSN:0301-1798
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:Major salivary glands play a role not only in digestion, but also in regulation of other functions in rodents. In this review, we analyzed and summarized the data about the rodents' parotid, submandibular and sublingual salivary glands functions, which is not limited to the production of saliva and action of its hydrolytic enzymes on food in the oral cavity. In recent decades significantly expanded understanding of major salivary glands nondigestive functions. They are involved in excretion of metabolic products, maintaining fluid and electrolyte balance. Special attention has been paid to the characteristics of specific (parotin, sialorphin, etc.) and nonspecific (epidermal growth factor, nerve growth factor, kallikrein, etc.) active substances of the major salivary glands and their involvement in wound healing, mineral metabolism, regulation of hematopoiesis and immunity system. Summarized and analyzed major salivary glands endocrine function in the organs and systems. Available literature data suggest: the structure of the major salivary glands, as well as the synthesis and secretion of a number of biologically active substances are controlled by sex hormones. In turn, these biologically active factors of the salivary glands, as epidermal growth factor, and parotin, sialorphin, whose expression is regulated by androgens, have an impact on the morphological and functional state of the gonads. Thus, major salivary glands operate a wide range of functions and involved in the regulation of sexual behavior of reproductive function and maintaining homeostasis in the body.
[Mh] Termos MeSH primário: Glândula Parótida/fisiologia
Roedores/fisiologia
Proteínas e Peptídeos Salivares/metabolismo
Glândula Sublingual/fisiologia
Glândula Submandibular/fisiologia
[Mh] Termos MeSH secundário: Animais
Fator de Crescimento Epidérmico/genética
Fator de Crescimento Epidérmico/metabolismo
Regulação da Expressão Gênica
Hormônios Esteroides Gonadais/genética
Hormônios Esteroides Gonadais/metabolismo
Hematopoese/fisiologia
Imunidade Inata/efeitos dos fármacos
Calicreínas/genética
Calicreínas/metabolismo
Fator de Crescimento Neural/genética
Fator de Crescimento Neural/metabolismo
Saliva/química
Saliva/fisiologia
Proteínas e Peptídeos Salivares/genética
Proteínas e Peptídeos Salivares/farmacologia
Equilíbrio Hidroeletrolítico/fisiologia
Cicatrização/efeitos dos fármacos
Cicatrização/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Gonadal Steroid Hormones); 0 (Salivary Proteins and Peptides); 62229-50-9 (Epidermal Growth Factor); 9061-61-4 (Nerve Growth Factor); EC 3.4.21.- (Kallikreins)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171229
[St] Status:MEDLINE


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[PMID]:29245340
[Au] Autor:Su CL; Chang GH; Fang KH; Chang CC
[Ad] Endereço:aDepartment of Surgery, Chang Gung Memorial Hospital, Linkou, TaoyuanbDepartment of Otolaryngology-Head and Neck SurgerycCenter of Excellence for Chang Gung Research Datalink, Chang Gung Memorial Hospital, ChiayidDepartment of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou, TaoyuaneDivision of Plastic and Reconstructive Surgery, Department of Surgery, China Medical University HospitalfSchool of medicine, College of Medicine, China Medical University, TaichunggInstitute of Imaging and Biomedical Photonics, National Chiao Tung University, Tainan, Taiwan.
[Ti] Título:Successful salvage for the intractable massive chylous leakage in a cirrhotic patient: A case report and literature review.
[So] Source:Medicine (Baltimore);96(49):e9103, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Iatrogenic chylous leakage (CL) is a rare but potentially life-threatening complication after neck surgery. In cirrhotic patient, the massive CL is even more intractable and extremely dangerous due to portal hypertension. PATIENTS CONCERNS: A 54-year-old liver cirrhotic patient had milky fluid leakage from left neck drainage tube after neck dissection surgery and hypopharyngeal cancer ablation. Electrolyte imbalance and shock status were reported when conservative managements and exploratory surgical repair failed to terminate the leakage. DIAGNOSIS: Massive CL up to >5 L/day was recorded on the post-operative day (POD) 9. INTERVENTIONS: A triangular-shaped pectoralis major (PM) muscle was designed to repair the lymph nodes dissected defect over left neck. OUTCOMES: After surgery, CL dramatically reduced to less than 300 mL/day in the coming day without relapses and terminated on the 8th days. After 3 months, the wound completely healed and the food conduit passage was patent without fistula. LESSONS: This report demonstrated the superiority of pectoralis major myocutaneous flap (PMMF) than the conservative treatment, local muscle flap, and radiologic or thoracoscopic duct ligation in cirrhotic patient with massive CL.
[Mh] Termos MeSH primário: Quilo
Cirrose Hepática/complicações
Esvaziamento Cervical/efeitos adversos
Complicações Pós-Operatórias/cirurgia
[Mh] Termos MeSH secundário: Ablação por Cateter
Seres Humanos
Neoplasias Hipofaríngeas/cirurgia
Masculino
Meia-Idade
Músculos Peitorais/transplante
Choque/complicações
Retalhos Cirúrgicos
Equilíbrio Hidroeletrolítico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009103


  7 / 24065 MEDLINE  
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[PMID]:29173350
[Au] Autor:Gupta S; Fenves AZ
[Ad] Endereço:Division of Nephrology, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, Mssachusetts.
[Ti] Título:The Distribution of Plasma Electrolytes.
[So] Source:Am J Med Sci;354(5):443-444, 2017 Nov.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Eletrólitos/sangue
Equilíbrio Hidroeletrolítico
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Masculino
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Electrolytes)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171206
[Lr] Data última revisão:
171206
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:28461222
[Au] Autor:Jørgensen LB; MacMillan HA; Overgaard J
[Ad] Endereço:Zoophysiology, Department of Bioscience, Aarhus University, C.F. Møllers Allé 3, Building 1131, 8000 Aarhus C, Denmark. Electronic address: lisa.b.joergensen@gmail.com.
[Ti] Título:Cold mortality is not caused by oxygen limitation or loss of ion homeostasis in the tropical freshwater shrimp Macrobrachium rosenbergii.
[So] Source:Cryobiology;76:146-149, 2017 Jun.
[Is] ISSN:1090-2392
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Using the tropical crustacean Macrobrachium rosenbergii we investigate two popular hypotheses proposed to explain loss of function in ectotherms exposed to critically high and low temperatures. Specifically, we examine whether acute cold stress disrupts hemolymph and muscle ion balance or causes a loss of oxygen availability. We found that acute cold stress causes loss of righting response at 13 °C, but that a cold-induced loss of ion-balance only occurs after onset of mortality. In regards to oxygen availability, we found no decrease in hemolymph oxygen content during cold exposure, and no changes in the concentrations of the anaerobic end products l-lactate and succinate in the tail muscle of the shrimp. Therefore, our results support neither of these two popular hypotheses and it remains unknown what physiological perturbations determine the lower limits of thermal tolerance in Macrobrachium rosenbergii.
[Mh] Termos MeSH primário: Temperatura Baixa/efeitos adversos
Palaemonidae/metabolismo
[Mh] Termos MeSH secundário: Animais
Hemolinfa/metabolismo
Homeostase
Ácido Láctico/metabolismo
Músculos/metabolismo
Oxigênio/metabolismo
Ácido Succínico/metabolismo
Equilíbrio Hidroeletrolítico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
33X04XA5AT (Lactic Acid); AB6MNQ6J6L (Succinic Acid); S88TT14065 (Oxygen)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  9 / 24065 MEDLINE  
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[PMID]:28974570
[Au] Autor:Selvarajah V; Mäki-Petäjä KM; Pedro L; Bruggraber SFA; Burling K; Goodhart AK; Brown MJ; McEniery CM; Wilkinson IB
[Ad] Endereço:From the Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, United Kingdom (V.S., K.M.M-P., A.K.G., C.M.M., I.B.W.); MRC Human Nutrition Unit, Cambridge, United Kingdom (L.P., S.F.A.B.); NIHR Cambridge Biomedical Research Centre, Core Biochemical Assay Laboratory, Uni
[Ti] Título:Novel Mechanism for Buffering Dietary Salt in Humans: Effects of Salt Loading on Skin Sodium, Vascular Endothelial Growth Factor C, and Blood Pressure.
[So] Source:Hypertension;70(5):930-937, 2017 Nov.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High dietary sodium intake triggers increased blood pressure (BP). Animal studies show that dietary salt loading results in dermal Na accumulation and lymphangiogenesis mediated by VEGF-C (vascular endothelial growth factor C), both attenuating the rise in BP. Our objective was to determine whether these mechanisms function in humans. We assessed skin electrolytes, BP, and plasma VEGF-C in 48 healthy participants randomized to placebo (70 mmol sodium/d) and slow sodium (200 mmol/d) for 7 days. Skin Na and K concentrations were measured in mg/g of wet tissue and expressed as the ratio Na :K to correct for variability in sample hydration. Skin Na :K increased between placebo and slow sodium phases (2.91±0.08 versus 3.12±0.09; =0.01). In post hoc analysis, there was a suggestion of a sex-specific effect, with a significant increase in skin Na :K in men (2.59±0.09 versus 2.88±0.12; =0.008) but not women (3.23±0.10 versus 3.36±0.12; =0.31). Women showed a significant increase in 24-hour mean BP with salt loading (93±1 versus 91±1 mm Hg; <0.001) while men did not (96±2 versus 96±2 mm Hg; =0.91). Skin Na :K correlated with BP, stroke volume, and peripheral vascular resistance in men but not in women. No change was noted in plasma VEGF-C. These findings suggest that the skin may buffer dietary Na , reducing the hemodynamic consequences of increased salt, and this may be influenced by sex.
[Mh] Termos MeSH primário: Dieta Hipossódica/métodos
Hipertensão
Potássio
Pele/metabolismo
Cloreto de Sódio
Sódio
Fator C de Crescimento do Endotélio Vascular/sangue
[Mh] Termos MeSH secundário: Adulto
Pressão Sanguínea/efeitos dos fármacos
Pressão Sanguínea/fisiologia
Método Duplo-Cego
Inglaterra
Feminino
Hemodinâmica/fisiologia
Seres Humanos
Hipertensão/diagnóstico
Hipertensão/dietoterapia
Hipertensão/metabolismo
Masculino
Meia-Idade
Potássio/análise
Potássio/metabolismo
Eliminação Renal/fisiologia
Fatores Sexuais
Sódio/análise
Sódio/metabolismo
Cloreto de Sódio/metabolismo
Cloreto de Sódio/farmacologia
Equilíbrio Hidroeletrolítico/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Vascular Endothelial Growth Factor C); 451W47IQ8X (Sodium Chloride); 9NEZ333N27 (Sodium); RWP5GA015D (Potassium)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.117.10003


  10 / 24065 MEDLINE  
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[PMID]:28920920
[Au] Autor:Shi G; Somlo DRM; Kim GH; Prescianotto-Baschong C; Sun S; Beuret N; Long Q; Rutishauser J; Arvan P; Spiess M; Qi L
[Ad] Endereço:Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
[Ti] Título:ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis.
[So] Source:J Clin Invest;127(10):3897-3912, 2017 10 02.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex. Serum hyperosmolality induces expression of both ERAD components and proAVP in AVP-producing neurons. Mice with global or AVP neuron-specific ablation of Se1L-Hrd1 ERAD progressively developed polyuria and polydipsia, characteristics of diabetes insipidus. Mechanistically, we found that ERAD deficiency causes marked ER retention and aggregation of a large proportion of all proAVP protein. Further, we show that proAVP is an endogenous substrate of Sel1L-Hrd1 ERAD. The inability to clear misfolded proAVP with highly reactive cysteine thiols in the absence of Sel1L-Hrd1 ERAD causes proAVP to accumulate and participate in inappropriate intermolecular disulfide-bonded aggregates, promoted by the enzymatic activity of protein disulfide isomerase (PDI). This study highlights a pathway linking ERAD to prohormone conformational maturation in neuroendocrine cells, expanding the role of ERAD in providing a conducive ER environment for nascent proteins to reach proper conformation.
[Mh] Termos MeSH primário: Degradação Associada com o Retículo Endoplasmático
Retículo Endoplasmático/metabolismo
Células Neuroendócrinas/metabolismo
Proteólise
Vasopressinas/metabolismo
Equilíbrio Hidroeletrolítico
[Mh] Termos MeSH secundário: Animais
Retículo Endoplasmático/genética
Camundongos
Camundongos Transgênicos
Células Neuroendócrinas/patologia
Neurônios/metabolismo
Neurônios/patologia
Polidipsia/genética
Polidipsia/metabolismo
Polidipsia/patologia
Isomerases de Dissulfetos de Proteínas/genética
Isomerases de Dissulfetos de Proteínas/metabolismo
Proteínas/genética
Proteínas/metabolismo
Ubiquitina-Proteína Ligases/genética
Ubiquitina-Proteína Ligases/metabolismo
Vasopressinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 0 (Sel1h protein, mouse); 0 (proAVP hormone); 11000-17-2 (Vasopressins); EC 2.3.2.27 (Syvn1 protein, mouse); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 5.3.4.1 (Protein Disulfide-Isomerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171114
[Lr] Data última revisão:
171114
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170919
[St] Status:MEDLINE



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