Base de dados : MEDLINE
Pesquisa : D08.811.913.050.612 [Categoria DeCS]
Referências encontradas : 479 [refinar]
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[PMID]:28468827
[Au] Autor:Zhao L; Fan J; Xia S; Pan Y; Liu S; Qian G; Qian Z; Kang HB; Arbiser JL; Pollack BP; Kudchadkar RR; Lawson DH; Rossi M; Abdel-Wahab O; Merghoub T; Khoury HJ; Khuri FR; Boise LH; Lonial S; Chen F; Chen J; Lin R
[Ad] Endereço:From the Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory, Emory University School of Medicine, Atlanta, Georgia 30322.
[Ti] Título:HMG-CoA synthase 1 is a synthetic lethal partner of BRAF in human cancers.
[So] Source:J Biol Chem;292(24):10142-10152, 2017 06 16.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Contributions of metabolic changes to cancer development and maintenance have received increasing attention in recent years. Although many human cancers share similar metabolic alterations, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Using an RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF up-regulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAF -dependent MEK1 activation in human cancer. Here, we identified HMG-CoA synthase 1 (HMGCS1), the upstream ketogenic enzyme of HMGCL, as an additional "synthetic lethal" partner of BRAF Although HMGCS1 expression did not correlate with BRAF mutation in human melanoma cells, HMGCS1 was selectively important for proliferation of BRAF -positive melanoma and colon cancer cells but not control cells harboring active N/KRAS mutants, and stable knockdown of HMGCS1 only attenuated colony formation and tumor growth potential of BRAF melanoma cells. Moreover, cytosolic HMGCS1 that co-localized with HMGCL and BRAF was more important than the mitochondrial HMGCS2 isoform in BRAF -expressing cancer cells in terms of acetoacetate production. Interestingly, HMGCL knockdown did not affect HMGCS1 expression levels, whereas HMGCS1 knockdown caused a compensating increase in HMGCL protein level because of attenuated protein degradation. However, this increase did not reverse the reduced ketogenesis in HMGCS1 knockdown cells. Mechanistically, HMGCS1 inhibition decreased intracellular acetoacetate levels, leading to reduced BRAF -MEK1 binding and consequent MEK1 activation. We conclude that the ketogenic HMGCS1-HMGCL-acetoacetate axis may represent a promising therapeutic target for managing BRAF -positive human cancers.
[Mh] Termos MeSH primário: Neoplasias do Colo/enzimologia
Hidroximetilglutaril-CoA Sintase/metabolismo
MAP Quinase Quinase 1/metabolismo
Melanoma/enzimologia
Proteínas de Neoplasias/metabolismo
Oxo-Ácido-Liases/metabolismo
Proteínas Proto-Oncogênicas B-raf/metabolismo
[Mh] Termos MeSH secundário: Acetoacetatos/metabolismo
Substituição de Aminoácidos
Animais
Linhagem Celular Tumoral
Proliferação Celular
Neoplasias do Colo/metabolismo
Neoplasias do Colo/patologia
Citosol/enzimologia
Citosol/metabolismo
Ativação Enzimática
Estabilidade Enzimática
Feminino
Seres Humanos
Hidroximetilglutaril-CoA Sintase/antagonistas & inibidores
Hidroximetilglutaril-CoA Sintase/genética
Isoenzimas/antagonistas & inibidores
Isoenzimas/genética
Isoenzimas/metabolismo
MAP Quinase Quinase 1/química
Melanoma/metabolismo
Melanoma/patologia
Camundongos Nus
Mutação
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Transplante de Neoplasias
Oxo-Ácido-Liases/antagonistas & inibidores
Oxo-Ácido-Liases/química
Oxo-Ácido-Liases/genética
Proteólise
Proteínas Proto-Oncogênicas B-raf/genética
Interferência de RNA
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acetoacetates); 0 (Isoenzymes); 0 (Neoplasm Proteins); 4ZI204Y1MC (acetoacetic acid); EC 2.3.3.10 (HMGCS1 protein, human); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 2.7.12.2 (MAP Kinase Kinase 1); EC 2.7.12.2 (MAP2K1 protein, human); EC 4.1.3.- (Oxo-Acid-Lyases); EC 4.1.3.4 (3-hydroxy-3-methylglutaryl-coenzyme A lyase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.788778


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[PMID]:28870788
[Au] Autor:Zawaski JA; Sabek OM; Voicu H; Eastwood Leung HC; Gaber MW
[Ad] Endereço:Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
[Ti] Título:Effect of Brain Tumor Presence During Radiation on Tissue Toxicity: Transcriptomic and Metabolic Changes.
[So] Source:Int J Radiat Oncol Biol Phys;99(4):983-993, 2017 Nov 15.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Radiation therapy (RT) causes functional and transcriptomic changes in the brain; however, most studies have been carried out in normal rodent brains. Here, the long-term effect of irradiation and tumor presence during radiation was investigated. METHODS AND MATERIALS: Male Wistar rats ∼7 weeks old were divided into 3 groups: sham implant, RT+sham implant, and RT+tumor implant (C6 glioma). Hypofractionated irradiation (8 or 6 Gy/day for 5 days) was localized to a 1-cm strip of cranium starting 5 days after implantation, resulting in complete tumor regression and prolonged survival. Biopsy of tissue was performed in the implant area 65 days after implantation. RNA was hybridized to GeneChip Rat Exon 1.0 ST array. Data were analyzed using significant analysis of microarrays and ingenuity pathway analysis. H magnetic resonance spectroscopy ( H-MRS) imaging was performed in the implantation site 65 to 70 days after implantation using a 9.4 T Biospec magnetic resonance imaging scanner with a quadrature rat brain array. Immunohistochemical staining for astrogliosis, HMG-CoA synthase 2, γ-aminobutyric acid (GABA) and taurine was performed at ∼65 days after implantation. RESULTS: Eighty-four genes had a false discovery rate <3.5%. We compared RT+tumor implant with RT+sham implant animals. The tumor presence affected networks associated with cancer/cell morphology/tissue morphology. H-MRS showed significant reduction in taurine levels (P<.04) at the implantation site in both groups. However, the RT+tumor group also showed significant increase in levels of neurotransmitter GABA (P=.02). Hippocampal taurine levels were only significantly reduced in the RT+tumor group (P=.03). HMG-CoA synthase 2, GABA and taurine levels were confirmed using staining. Glial fibrillary acidic protein staining demonstrated a significant increase in inflammation that was heightened in the RT+tumor group. CONCLUSIONS: Our data indicate that tumor presence during radiation significantly affects long-term functional transcriptomics landscape and neurotransmitter levels at the tumor implantation site/normal tissue, accompanied by increased inflammation (astrogliosis).
[Mh] Termos MeSH primário: Neoplasias Encefálicas/radioterapia
Encéfalo/efeitos da radiação
Glioma/radioterapia
Neurotransmissores/análise
Lesões Experimentais por Radiação/metabolismo
[Mh] Termos MeSH secundário: Aloenxertos
Animais
Biópsia
Encéfalo/metabolismo
Encéfalo/patologia
Neoplasias Encefálicas/química
Neoplasias Encefálicas/patologia
Radioterapia Hipofracionada
Perfilação da Expressão Gênica
Glioma/química
Glioma/patologia
Gliose/metabolismo
Gliose/patologia
Hipocampo/química
Hipocampo/patologia
Hipocampo/efeitos da radiação
Hidroximetilglutaril-CoA Sintase/análise
Imagem por Ressonância Magnética/métodos
Espectroscopia de Ressonância Magnética
Masculino
Transplante de Neoplasias
Neurotransmissores/metabolismo
Lesões Experimentais por Radiação/patologia
Ratos
Ratos Wistar
Taurina/análise
Fatores de Tempo
Análise Serial de Tecidos/métodos
Ácido gama-Aminobutírico/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neurotransmitter Agents); 1EQV5MLY3D (Taurine); 56-12-2 (gamma-Aminobutyric Acid); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170906
[St] Status:MEDLINE


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[PMID]:28867541
[Au] Autor:Su SG; Yang M; Zhang MF; Peng QZ; Li MY; Liu LP; Bao SY
[Ad] Endereço:Department of Pathology, Hexian Memorial Hospital of Panyu District, Guangzhou, China.
[Ti] Título:miR-107-mediated decrease of HMGCS2 indicates poor outcomes and promotes cell migration in hepatocellular carcinoma.
[So] Source:Int J Biochem Cell Biol;91(Pt A):53-59, 2017 Oct.
[Is] ISSN:1878-5875
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) has been implicated in human cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we show that HMGCS2 is downregulated and exhibits antimetastatic potential in HCC. Low expression of HMGCS2 was associated with poor tumor differentiation, vascular invasion and worse overall and disease-free survivals in two independent cohorts consisting of 743 cases. In vitro data demonstrated HMGCS2 overexpression suppressed, whereas HMGCS2 silence promoted HCC cell migration via Epithelial-Mesenchymal Transition (EMT) process and the activation of ERK/c-Jun signaling pathway. Inhibition of ERK phosphorylation by PD098059 markedly attenuated the malignant phenotypes mediated by HMGCS2 siRNA. Furthermore, miR-107 was identified as an upstream regulator of HMGCS2 via directly targeting the 3'-UTR of HMGCS2 mRNA. Collectively, our findings suggest HMGCS2 serve as a promising prognostic biomarker and exert anti-tumor activity towards HCC, and therefore provide a potential target for HCC clinical intervention.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular/diagnóstico
Carcinoma Hepatocelular/patologia
Movimento Celular/genética
Hidroximetilglutaril-CoA Sintase/metabolismo
Neoplasias Hepáticas/diagnóstico
Neoplasias Hepáticas/patologia
MicroRNAs/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Sequência de Bases
Carcinoma Hepatocelular/genética
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Regulação Neoplásica da Expressão Gênica/genética
Seres Humanos
Hidroximetilglutaril-CoA Sintase/genética
Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo
Neoplasias Hepáticas/genética
Sistema de Sinalização das MAP Quinases/genética
Masculino
Meia-Idade
Prognóstico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGCS2 protein, human); 0 (MIRN107 microRNA, human); 0 (MicroRNAs); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


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[PMID]:28686747
[Au] Autor:Quintana AM; Hernandez JA; Gonzalez CG
[Ad] Endereço:Department of Biological Sciences, University of Texas El Paso, El Paso, TX, United States of America.
[Ti] Título:Functional analysis of the zebrafish ortholog of HMGCS1 reveals independent functions for cholesterol and isoprenoids in craniofacial development.
[So] Source:PLoS One;12(7):e0180856, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There are 8 different human syndromes caused by mutations in the cholesterol synthesis pathway. A subset of these disorders such as Smith-Lemli-Opitz disorder, are associated with facial dysmorphia. However, the molecular and cellular mechanisms underlying such facial deficits are not fully understood, primarily because of the diverse functions associated with the cholesterol synthesis pathway. Recent evidence has demonstrated that mutation of the zebrafish ortholog of HMGCR results in orofacial clefts. Here we sought to expand upon these data, by deciphering the cholesterol dependent functions of the cholesterol synthesis pathway from the cholesterol independent functions. Moreover, we utilized loss of function analysis and pharmacological inhibition to determine the extent of sonic hedgehog (Shh) signaling in animals with aberrant cholesterol and/or isoprenoid synthesis. Our analysis confirmed that mutation of hmgcs1, which encodes the first enzyme in the cholesterol synthesis pathway, results in craniofacial abnormalities via defects in cranial neural crest cell differentiation. Furthermore targeted pharmacological inhibition of the cholesterol synthesis pathway revealed a novel function for isoprenoid synthesis during vertebrate craniofacial development. Mutation of hmgcs1 had no effect on Shh signaling at 2 and 3 days post fertilization (dpf), but did result in a decrease in the expression of gli1, a known Shh target gene, at 4 dpf, after morphological deficits in craniofacial development and chondrocyte differentiation were observed in hmgcs1 mutants. These data raise the possibility that deficiencies in cholesterol modulate chondrocyte differentiation by a combination of Shh independent and Shh dependent mechanisms. Moreover, our results describe a novel function for isoprenoids in facial development and collectively suggest that cholesterol regulates craniofacial development through versatile mechanisms.
[Mh] Termos MeSH primário: Colesterol/biossíntese
Anormalidades Craniofaciais/genética
Proteínas Hedgehog/genética
Hidroximetilglutaril-CoA Redutases/genética
Hidroximetilglutaril-CoA Sintase/genética
Terpenos/metabolismo
Proteínas de Peixe-Zebra/genética
Proteína GLI1 em Dedos de Zinco/genética
[Mh] Termos MeSH secundário: Animais
Anticolesterolemiantes/farmacologia
Atorvastatina Cálcica/farmacologia
Benzofenonas/farmacologia
Padronização Corporal/efeitos dos fármacos
Padronização Corporal/genética
Diferenciação Celular/efeitos dos fármacos
Condrócitos/efeitos dos fármacos
Condrócitos/metabolismo
Condrócitos/patologia
Anormalidades Craniofaciais/metabolismo
Anormalidades Craniofaciais/patologia
Embrião não Mamífero
Inibidores Enzimáticos/farmacologia
Regulação da Expressão Gênica no Desenvolvimento
Proteínas Hedgehog/metabolismo
Seres Humanos
Hidroximetilglutaril-CoA Redutases/metabolismo
Hidroximetilglutaril-CoA Sintase/metabolismo
Crista Neural/efeitos dos fármacos
Crista Neural/metabolismo
Crista Neural/patologia
Piperidinas/farmacologia
Piridinas/farmacologia
Transdução de Sinais
Terpenos/antagonistas & inibidores
Peixe-Zebra
Proteínas de Peixe-Zebra/metabolismo
Proteína GLI1 em Dedos de Zinco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anticholesteremic Agents); 0 (Benzophenones); 0 (Enzyme Inhibitors); 0 (Hedgehog Proteins); 0 (Piperidines); 0 (Pyridines); 0 (Shha protein, zebrafish); 0 (Terpenes); 0 (Zebrafish Proteins); 0 (Zinc Finger Protein GLI1); 161582-11-2 (Ro 48-8071); 48A5M73Z4Q (Atorvastatin Calcium); 97C5T2UQ7J (Cholesterol); EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases); EC 2.3.3.10 (HMGCS1 protein, human); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); IOW153004F (lonafarnib)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170708
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180856


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[PMID]:28320515
[Au] Autor:Hu LT; Zhu BL; Lai YJ; Long Y; Zha JS; Hu XT; Zhang JH; Chen GJ
[Ad] Endereço:Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 Youyi Road, Chongqing 400016, China; Department of Neurology, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical College, Nanchong 637000, Sic
[Ti] Título:HMGCS2 promotes autophagic degradation of the amyloid-ß precursor protein through ketone body-mediated mechanisms.
[So] Source:Biochem Biophys Res Commun;486(2):492-498, 2017 Apr 29.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:HMGCS2 (mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2) is a control enzyme in ketogenesis. The mitochondrial localization and interaction with APP (ß-amyloid precursor protein) suggest that HMGCS2 may play a role in the pathophysiology of AD (Alzheimer's disease). Here we report that overexpression of HMGCS2 decreased levels of APP and related CTFs (carboxy-terminal fragments), which was largely prevented by an autophagic inhibitor chloroquine. In addition, HMGCS2 enhancement of autophagic marker LC3II was diminished by rapamycin, an inhibitor of mechanistic target of rapamycin. Moreover, deprivation of EBSS (Earle's Balanced Salt Solution) significantly augmented the effect of HMGCS2 on LC3II, while acetoacetate reversed the reduction of LC3II, APP and CTFs which was induced by HMGCS2 knockdown. In the presence of acetoacetate, rapamycin failed to induce further increase of LC3II, which mimicked the effect of HMGCS2 overexpression. Finally, HMGCS2 enhanced the antioxidant response. Collectively, HMGCS2 shares with ketone bodies common features in autophagic clearance of APP and CTFs, suggesting that ketone bodies play an important role in HMGCS2 regulation of the autophagy.
[Mh] Termos MeSH primário: Precursor de Proteína beta-Amiloide/metabolismo
Autofagia/genética
Hidroximetilglutaril-CoA Sintase/genética
Corpos Cetônicos/metabolismo
Proteínas Associadas aos Microtúbulos/genética
Serina-Treonina Quinases TOR/genética
[Mh] Termos MeSH secundário: Acetoacetatos/farmacologia
Animais
Linhagem Celular
Cloroquina/farmacologia
Regulação da Expressão Gênica
Células HEK293
Hipocampo/citologia
Hipocampo/efeitos dos fármacos
Hipocampo/metabolismo
Seres Humanos
Hidroximetilglutaril-CoA Sintase/antagonistas & inibidores
Hidroximetilglutaril-CoA Sintase/metabolismo
Camundongos
Proteínas Associadas aos Microtúbulos/metabolismo
Neurônios/citologia
Neurônios/efeitos dos fármacos
Neurônios/metabolismo
Proteólise/efeitos dos fármacos
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Transdução de Sinais
Sirolimo/farmacologia
Serina-Treonina Quinases TOR/antagonistas & inibidores
Serina-Treonina Quinases TOR/metabolismo
Transgenes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetoacetates); 0 (Amyloid beta-Protein Precursor); 0 (HMGCS2 protein, human); 0 (Ketone Bodies); 0 (MAP1LC3A protein, human); 0 (Microtubule-Associated Proteins); 0 (RNA, Small Interfering); 0 (Recombinant Proteins); 4ZI204Y1MC (acetoacetic acid); 886U3H6UFF (Chloroquine); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); W36ZG6FT64 (Sirolimus)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170605
[Lr] Data última revisão:
170605
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE


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[PMID]:27874312
[Au] Autor:Kang DY; S P N; Darvin P; Joung YH; Byun HJ; Do CH; Park KD; Park MN; Cho KH; Yang YM
[Ad] Endereço:a Department of Pathology, School of Medicine , Institute of Biomedical Science and Technology, Konkuk University , Seoul , Korea.
[Ti] Título:Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.
[So] Source:Anim Biotechnol;28(3):189-197, 2017 Jul 03.
[Is] ISSN:1532-2378
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.
[Mh] Termos MeSH primário: Angiopoietinas/metabolismo
Diterpenos/farmacologia
Hidroximetilglutaril-CoA Sintase/antagonistas & inibidores
Cetose/metabolismo
Lactonas/farmacologia
Lipase Lipoproteica/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Hidroximetilglutaril-CoA Sintase/metabolismo
Corpos Cetônicos/metabolismo
Camundongos
Modelos Biológicos
Fator de Transcrição STAT5/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiopoietins); 0 (Diterpenes); 0 (Ketone Bodies); 0 (Lactones); 0 (STAT5 Transcription Factor); 0 (momilactone B); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 3.1.1.34 (Lipoprotein Lipase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE
[do] DOI:10.1080/10495398.2016.1252769


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[PMID]:27845231
[Au] Autor:Cook GA; Lavrentyev EN; Pham K; Park EA
[Ad] Endereço:Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, United States. Electronic address: gcook@uthsc.edu.
[Ti] Título:Streptozotocin diabetes increases mRNA expression of ketogenic enzymes in the rat heart.
[So] Source:Biochim Biophys Acta;1861(2):307-312, 2017 02.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Diabetic cardiomyopathy develops in insulin-dependent diabetic patients who have no hypertension, cardiac hypertrophy or vascular disease. Diabetes increases cardiac fatty acid oxidation, but cardiac hypertrophy limits fatty acid oxidation. Here we examined effects of diabetes on gene expression in rat hearts. METHODS: We used oligonucleotide microarrays to examine effects of insulindependent diabetes in the rat heart. RTQ PCR confirmed results of microarrays. Specific antibodies were used to examine changes in the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). RESULTS: A surprising result of diabetes was increased mRNA encoding all enzymes of the ketone body synthesis pathway. Increased mRNA expression for these enzymes was confirmed by RTQ PCR. The mRNA encoding HMGCS2, the rate-controlling enzyme, was 27 times greater in diabetic hearts. Total HMGCS2 protein increased 8-fold in diabetic hearts, but no difference was found in HMGCS2 protein in control vs. diabetic liver. CONCLUSIONS: Insulin-dependent diabetes induced the enzymes of ketone body synthesis in the heart, including HMGCS2, as well as increasing enzymes of fatty acid oxidation. GENERAL SIGNIFICANCE: The mammalian heart does not export ketone bodies to other tissues, but rather is a major consumer of ketone bodies. Induction of HMGCS2, which is normally expressed only in the fetal and newborn heart, may indicate an adaptation by the heart to combat "metabolic inflexibility" by shifting the flux of excess intramitochondrial acetyl-CoA derived from elevated fatty acid oxidation into ketone bodies, liberating free CoA to balance the acetyl-CoA/CoA ratio in favor of increased glucose oxidation through the pyruvate dehydrogenase complex.
[Mh] Termos MeSH primário: Acil Coenzima A/genética
Diabetes Mellitus Experimental/induzido quimicamente
Diabetes Mellitus Experimental/genética
Hidroximetilglutaril-CoA Sintase/genética
Miocárdio/metabolismo
RNA Mensageiro/genética
Estreptozocina/farmacologia
[Mh] Termos MeSH secundário: Animais
Cardiomiopatias Diabéticas/genética
Cardiomiopatias Diabéticas/metabolismo
Ácidos Graxos/metabolismo
Expressão Gênica/genética
Coração/fisiopatologia
Insulina/metabolismo
Corpos Cetônicos/metabolismo
Mitocôndrias/metabolismo
Oxirredução
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Fatty Acids); 0 (Insulin); 0 (Ketone Bodies); 0 (RNA, Messenger); 1553-55-5 (3-hydroxy-3-methylglutaryl-coenzyme A); 5W494URQ81 (Streptozocin); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161116
[St] Status:MEDLINE


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[PMID]:27816970
[Au] Autor:Chen SW; Chou CT; Chang CC; Li YJ; Chen ST; Lin IC; Kok SH; Cheng SJ; Lee JJ; Wu TS; Kuo ML; Lin BR
[Ad] Endereço:Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan.
[Ti] Título:HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer.
[So] Source:Oncotarget;8(14):22460-22476, 2017 Apr 04.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/metabolismo
Neoplasias Colorretais/metabolismo
Hidroximetilglutaril-CoA Sintase/metabolismo
Mitocôndrias/fisiologia
Neoplasias Bucais/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinoma de Células Escamosas/diagnóstico
Carcinoma de Células Escamosas/mortalidade
Movimento Celular
Neoplasias Colorretais/diagnóstico
Neoplasias Colorretais/mortalidade
Feminino
Seres Humanos
Hidroximetilglutaril-CoA Sintase/genética
Camundongos
Camundongos SCID
Neoplasias Bucais/diagnóstico
Neoplasias Bucais/mortalidade
PPAR alfa/metabolismo
Prognóstico
Proteínas Proto-Oncogênicas pp60(c-src)/genética
Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
RNA Interferente Pequeno/genética
Análise de Sobrevida
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HMGCS2 protein, human); 0 (PPAR alpha); 0 (RNA, Small Interfering); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161107
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.13006


  9 / 479 MEDLINE  
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[PMID]:26578529
[Au] Autor:Jiménez MJ; Bocos C; Panadero M; Herrera E
[Ad] Endereço:Departamento de Química y Bioquímica, Universidad San Pablo CEU, Ctra. Boadilla del Monte km 5.3, Boadilla del Monte, 28668, Madrid, Spain.
[Ti] Título:Fish oil diet in pregnancy and lactation reduces pup weight and modifies newborn hepatic metabolic adaptations in rats.
[So] Source:Eur J Nutr;56(1):409-420, 2017 Feb.
[Is] ISSN:1436-6215
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To determine the effects of a diet containing fish oil (FD) during pregnancy and lactation in rats on the metabolic adaptations made by the offspring during early extrauterine life and to compare it to an olive oil diet (OD). METHODS: Rats were mated and randomly allocated to OD or FD containing 10 % of the corresponding oil. During lactation, litters were adjusted to eight pups per dam. Fetuses of 20 days and pups of 0, 1, 10, 20 and 30 days of age were studied. RESULTS: Body weight and length were lower in pups of the FD group from birth. The diet, milk, pups' plasma and liver of FD group had higher proportions of n-3 LCPUFA, but the content of arachidonic acid (ARA) was lower. Plasma glucose was higher, but unesterified fatty acids, triacylglycerols (TAG), 3-hydroxybutyrate and liver TAG in 1-day-old pups were lower in the FD group, and differences in some of these variables were also found in pups up to 30 days old. Liver lipoprotein lipase activity and mRNA expression, and the expression of carnitine palmitoyl transferase I, acyl-CoA oxidase and 3-hydroxy 3-methyl glutaryl-CoA synthase increased more at birth in pups of the FD group, but the expression of sterol regulatory element binding protein-1c and Δ6-desaturase mRNA was lower in the FD group. CONCLUSIONS: Maternal intake of high n-3 LCPUFA retards postnatal development, which could be the result of impaired ARA synthesis, and affects hepatic metabolic adaptations to extrauterine life.
[Mh] Termos MeSH primário: Dieta
Óleos de Peixe/administração & dosagem
Lactação
Fenômenos Fisiológicos da Nutrição Materna
[Mh] Termos MeSH secundário: Ácido 3-Hidroxibutírico/sangue
Acil-CoA Oxidase/genética
Acil-CoA Oxidase/metabolismo
Animais
Animais Recém-Nascidos
Ácido Araquidônico/administração & dosagem
Ácido Araquidônico/sangue
Glicemia
Carnitina O-Palmitoiltransferase/genética
Carnitina O-Palmitoiltransferase/metabolismo
Ácidos Graxos/sangue
Ácidos Graxos Ômega-3/administração & dosagem
Feminino
Óleos de Peixe/análise
Hidroximetilglutaril-CoA Sintase/genética
Hidroximetilglutaril-CoA Sintase/metabolismo
Lipase Lipoproteica/genética
Lipase Lipoproteica/metabolismo
Fígado/efeitos dos fármacos
Fígado/metabolismo
Azeite de Oliva/administração & dosagem
Azeite de Oliva/análise
Gravidez
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Ratos
Ratos Sprague-Dawley
Estearoil-CoA Dessaturase/genética
Estearoil-CoA Dessaturase/metabolismo
Proteína de Ligação a Elemento Regulador de Esterol 1/genética
Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
Triglicerídeos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Fatty Acids); 0 (Fatty Acids, Omega-3); 0 (Fish Oils); 0 (Olive Oil); 0 (RNA, Messenger); 0 (Srebf1 protein, rat); 0 (Sterol Regulatory Element Binding Protein 1); 0 (Triglycerides); 27YG812J1I (Arachidonic Acid); EC 1.14.19.1 (Stearoyl-CoA Desaturase); EC 1.14.99.- (delta 6-desaturase, rat); EC 1.3.3.6 (Acyl-CoA Oxidase); EC 2.3.1.21 (Carnitine O-Palmitoyltransferase); EC 2.3.1.21 (carnitine palmitoyltransferase-1a, rat); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase); EC 3.1.1.34 (Lipoprotein Lipase); TZP1275679 (3-Hydroxybutyric Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151119
[St] Status:MEDLINE
[do] DOI:10.1007/s00394-015-1091-y


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[PMID]:27744449
[Au] Autor:Li L; Li Y; Dai Z; Liu M; Wang B; Liu S; Wang L; Chen L; Tan Y; Wu G
[Ad] Endereço:Dept. of Vasculocardiology, Xiangya Hospital, Changsha, Hunan, China.
[Ti] Título:Lipid Metabolism in Vascular Smooth Muscle Cells Infuenced by HCMV Infection.
[So] Source:Cell Physiol Biochem;39(5):1804-1812, 2016.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The present study was designed to observe the infection of human cytomegalovirus (HCMV) to human vascular smooth muscle cells (VSMCs), and the effect of viral infection on lipid metabolism in VSMCs. METHODS: The cytopathic effects were observed by inverted microscopy and viral infection were examined by electron microscopy and RT-PCR. The lipid metabolism related gene profiling of VSMCs after HCMV infection was assayed by cDNA assay and the abnormal expression of genes were validated by quantitative RT-PCR. The content of cholesterol in VSMCs after HCMV infection was assayed by cholesterol detection kit. RESULTS: VSMCs showed obvious cytopathic effects after HCMV infection. Intact viral particles could be detected in VSMCs using electron microscope. By use of RT-PCR technology, IE gene of HCMV could be amplified from VSMCs. The expression of cell lipid metabolism related gene profiling showed obvious disorders. The expression levels of HMG-CoA synthase and HMG-CoA reductase after infection increased significantly. The cellular cholesterol content (µmol/106 cells) was significantly higher than that of mock infected group at 72h post infection. CONCLUSION: HCMV can infect VSMCs and the infection can affect cellular lipid metabolism related gene expression, which get involved in the occurrence and development of atherosclerosis (AS).
[Mh] Termos MeSH primário: Colesterol/metabolismo
Hidroximetilglutaril-CoA Sintase/genética
Metabolismo dos Lipídeos/genética
Miócitos de Músculo Liso/metabolismo
Oxirredutases/genética
[Mh] Termos MeSH secundário: Células Cultivadas
Citomegalovirus/patogenicidade
Citomegalovirus/fisiologia
Perfilação da Expressão Gênica
Regulação da Expressão Gênica
Interações Hospedeiro-Patógeno
Seres Humanos
Hidroximetilglutaril-CoA Sintase/metabolismo
Músculo Liso Vascular/metabolismo
Músculo Liso Vascular/virologia
Miócitos de Músculo Liso/virologia
Oxirredutases/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
97C5T2UQ7J (Cholesterol); EC 1.- (Oxidoreductases); EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170207
[Lr] Data última revisão:
170207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161017
[St] Status:MEDLINE



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