Base de dados : MEDLINE
Pesquisa : D01.210.450.150.450 [Categoria DeCS]
Referências encontradas : 3439 [refinar]
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[PMID]:29274777
[Au] Autor:Tong M; He Z; Lin X; Zhou Y; Wang Q; Zheng Z; Chen J; Xu H; Tian N
[Ad] Endereço:Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.
[Ti] Título:Lithium chloride contributes to blood-spinal cord barrier integrity and functional recovery from spinal cord injury by stimulating autophagic flux.
[So] Source:Biochem Biophys Res Commun;495(4):2525-2531, 2018 01 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) significantly compromises functional neuronal recovery. Autophagy is a potential therapeutic target when seeking to protect the BSCB. We explored the effects of lithium chloride (LiCl) on BSCB permeability and autophagy-induced SCI both in a rat model of SCI and in endothelial cells subjected to oxygen-glucose deprivation. We evaluated BSCB status using the Evans Blue dye extravasation test and measurement of tight junction (TJ) protein levels; we also assessed functional locomotor recovery. We detected autophagy-associated proteins in vivo and in vitro using both Western blotting and immunofluorescence staining. We found that, in a rat model of SCI, LiCl attenuated the elevation in BSCB permeability, improved locomotor recovery, and inhibited the degradation of TJ proteins including occludin and claudin-5. LiCl significantly induced the extent of autophagic flux after SCI by increasing LC3-II and ATG-5 levels, and abolishing p62 accumulation. In addition, a combination of LiCl and the autophagy inhibitor chloroquine not only partially eliminated the BSCB-protective effect of LiCl, but also exacerbated TJ protein degradation both in vivo and in vitro. Together, these findings suggest that LiCl treatment alleviates BSCB disruption and promotes locomotor recovery after SCI, partly by stimulating autophagic flux.
[Mh] Termos MeSH primário: Proteínas Relacionadas à Autofagia/metabolismo
Autofagia/efeitos dos fármacos
Barreira Hematoencefálica/efeitos dos fármacos
Cloreto de Lítio/administração & dosagem
Traumatismos da Medula Espinal/tratamento farmacológico
Traumatismos da Medula Espinal/fisiopatologia
Regeneração da Medula Espinal/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Barreira Hematoencefálica/patologia
Barreira Hematoencefálica/fisiopatologia
Relação Dose-Resposta a Droga
Feminino
Fármacos Neuroprotetores/administração & dosagem
Ratos
Ratos Sprague-Dawley
Recuperação de Função Fisiológica/efeitos dos fármacos
Recuperação de Função Fisiológica/fisiologia
Traumatismos da Medula Espinal/patologia
Regeneração da Medula Espinal/fisiologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Autophagy-Related Proteins); 0 (Neuroprotective Agents); G4962QA067 (Lithium Chloride)
[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:171225
[St] Status:MEDLINE


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[PMID]:29431064
[Au] Autor:Mathuram TL; Ravikumar V; Reece LM; Sasikumar CS; Cherian KM
[Ad] Endereço:Department of Stem Cell and Tissue Engineering, Frontier Mediville (A Unit of Frontier Lifeline and Dr. K. M. Cherian Heart Foundation), Affiliated to University of Madras, Chennai-601201, Tamil Nadu, India.
[Ti] Título:Correlative Studies Unravelling the Possible Mechanism of Cell Death in Tideglusib-Treated Human Ovarian Teratocarcinoma-Derived PA-1 Cells.
[So] Source:J Environ Pathol Toxicol Oncol;36(4):321-344, 2017.
[Is] ISSN:2162-6537
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study aims to unravel the use of GSK-3 inhibitors as viable apoptotic inducers for teratocarcinoma-derived ovarian PA-1 cells. MTT assay was carried out to assess inhibitory concentrations of LiCl and TDG. AO/EB staining and Hoechst 33258 staining were employed to assess the damage. Mitochondrial membrane potential (ΔΨm) and ROS generation were assessed with IC50 concentrations of LiCl and TDG. Tumor-related genes (p53, p21, IL-8, TNF-α, MMP-2, Fas-L, Cox-2, and caspase-3) were assessed with 1/4 IC50, 1/2 IC50, IC50 concentrations by semi-quantitative RT- PCR. Cell cycle analysis was performed with IC50 concentration of LiCl and TDG. Western blot analysis was performed for caspase-3, caspase-7, caspase-9, PARP to estimate the possible damage induced by GSK-3 inhibitors and regulation of GSK-3ß, pGSK-3ß, Cox-2. GSK-3 inhibitors demonstrated a concentration and time-dependent reduction in cell viability, exhibiting significant ROS generation and reduced ΔΨm at their IC50 values. Substantial concentration-dependent gene expression changes with significant upregulation of P21, Cox-2, TNF-α, caspase-3, Fas-L were observed. Protein expression of caspase-3 caspase-7, caspase-9, PARP exhibited significant cleavage in LiCl and TDG-treated cells. Protein expression of Cox-2 was significantly increased in IC50 concentration of TDG. Cell cycle analysis showed significant accumulation of cells at sub-G0-G1.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Quinase 3 da Glicogênio Sintase/antagonistas & inibidores
Neoplasias Ovarianas/tratamento farmacológico
Teratocarcinoma/tratamento farmacológico
Tiadiazóis/farmacologia
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Inibidor de Quinase Dependente de Ciclina p21/genética
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Cloreto de Lítio/farmacologia
Metaloproteinase 2 da Matriz/genética
Potencial da Membrana Mitocondrial
Neoplasias Ovarianas/patologia
Espécies Reativas de Oxigênio/metabolismo
Teratocarcinoma/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CDKN1A protein, human); 0 (Cyclin-Dependent Kinase Inhibitor p21); 0 (NP 031112); 0 (Reactive Oxygen Species); 0 (Thiadiazoles); EC 2.7.11.26 (Glycogen Synthase Kinase 3); EC 3.4.24.24 (Matrix Metalloproteinase 2); G4962QA067 (Lithium Chloride)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.1615/JEnvironPatholToxicolOncol.2017025018


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[PMID]:29330051
[Au] Autor:Li X; Lu Q; Xie W; Wang Y; Wang G
[Ad] Endereço:Department of Orthopedics, Wuhan 672 Integrated Traditional Chinese and Western Medicine Hospital, Wuhan, 430079, Hubei, China. Electronic address: lixuguiwuhan@sina.com.
[Ti] Título:Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/ß-Catenin signaling.
[So] Source:Biochem Biophys Res Commun;496(2):443-449, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Osteosarcoma is a common malignant bone tumor occurring in adolescents and children. The poor prognosis and low 5-year survival rate of osteosarcoma partly due to high metastasis of osteosarcoma. Triptolide (TPL), an extract from Tripterygium wilfordii, is widely used in cancer treatment. In our present study, we aimed to study the effect of TPL in osteosarcoma treatment and explore the associated regulation mechanism. Our study revealed that TPL inhibited angiogenesis by suppressing the expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in dose dependent manner. Besides, cell apoptosis was induced by TPL obviously in dose dependent manner. Further study demonstrated that TPL induced obvious cell autophagy with increased concentration. The cooperation of autophagy inhibitor 3-MA abolished the effect of TPL on anti-angiogenesis and apoptosis promoting. Moreover, we found that Wnt/ß-Catenin signaling was inactivated by TPL and the adding of pathway inducer Licl neutralized the effect of TPL on autophagy induction, anti-angiogenesis and apoptosis promoting. Taken together, we suggested that TPL inhibited angiogenesis and induced cell apoptosis in osteosarcoma cells by inducing autophagy via repressing Wnt/ß-Catenin signaling.
[Mh] Termos MeSH primário: Antineoplásicos Alquilantes/farmacologia
Autofagia/efeitos dos fármacos
Diterpenos/farmacologia
Regulação Neoplásica da Expressão Gênica
Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores
Fenantrenos/farmacologia
Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adenina/análogos & derivados
Adenina/farmacologia
Apoptose/efeitos dos fármacos
Autofagia/genética
Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Compostos de Epóxi/farmacologia
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Cloreto de Lítio/farmacologia
Osteoblastos/efeitos dos fármacos
Osteoblastos/metabolismo
Osteoblastos/patologia
Transdução de Sinais
Fator A de Crescimento do Endotélio Vascular/genética
Fator A de Crescimento do Endotélio Vascular/metabolismo
beta Catenina/genética
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 0 (CTNNB1 protein, human); 0 (Diterpenes); 0 (Epoxy Compounds); 0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Phenanthrenes); 0 (VEGFA protein, human); 0 (Vascular Endothelial Growth Factor A); 0 (beta Catenin); 19ALD1S53J (triptolide); 5142-23-4 (3-methyladenine); G4962QA067 (Lithium Chloride); JAC85A2161 (Adenine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180114
[St] Status:MEDLINE


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[PMID]:29190615
[Au] Autor:Yang K; Chen Z; Gao J; Shi W; Li L; Jiang S; Hu H; Liu Z; Xu D; Wu L
[Ad] Endereço:College of Pharmacy, Gannan Medical University, Ganzhou, China.
[Ti] Título:The Key Roles of GSK-3ß in Regulating Mitochondrial Activity.
[So] Source:Cell Physiol Biochem;44(4):1445-1459, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Glycogen synthase kinase-3ß (GSK-3ß), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3ß may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3ß has been implicated in mediation of mitochondrial functions. GSK-3ß exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3ß might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3ß inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Intensive efforts have been made for exploring GSK-3ß inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3ß. The key roles of GSK-3ß in mediation of mitochondrial functions are discussed in this review.
[Mh] Termos MeSH primário: Glicogênio Sintase Quinase 3 beta/metabolismo
Mitocôndrias/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/tratamento farmacológico
Animais
Apoptose/efeitos dos fármacos
Produtos Biológicos/farmacologia
Produtos Biológicos/uso terapêutico
Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores
Glicogênio Sintase Quinase 3 beta/química
Cloreto de Lítio/farmacologia
Cloreto de Lítio/uso terapêutico
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Mitocôndrias/efeitos dos fármacos
Proteínas Mitocondriais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biological Products); 0 (Mitochondrial Proteins); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); G4962QA067 (Lithium Chloride)
[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:171201
[St] Status:MEDLINE
[do] DOI:10.1159/000485580


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[PMID]:29244860
[Au] Autor:de Groot T; Damen L; Kosse L; Alsady M; Doty R; Baumgarten R; Sheehan S; van der Vlag J; Korstanje R; Deen PMT
[Ad] Endereço:The Jackson Laboratory, Bar Harbor, Maine, United States of America.
[Ti] Título:Lithium reduces blood glucose levels, but aggravates albuminuria in BTBR-ob/ob mice.
[So] Source:PLoS One;12(12):e0189485, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy. Twelve-week old female BTBR-ob/ob mice were treated for 12 weeks with 0, 10 and 40 mmol LiCl/kg after which the development of diabetes and diabetic nephropathy were analysed. In comparison to BTBR-WT mice, ob/ob mice demonstrated elevated bodyweight, increased blood glucose/insulin levels, urinary albumin and immunoglobulin G levels, glomerulosclerosis, reduced nephrin abundance and a damaged proximal tubule brush border. The lithium-10 and -40 diets did not affect body weight and resulted in blood lithium levels of respectively <0.25 mM and 0.48 mM. The Li-40 diet fully rescued the elevated non-fasting blood glucose levels. Importantly, glomerular filtration rate was not affected by lithium, while urine albumin and immunoglobulin G content were further elevated. While lithium did not worsen the glomerulosclerosis, proximal tubule function seemed affected by lithium, as urinary NGAL levels were significantly increased. These results demonstrate that lithium attenuates non-fasting blood glucose levels in diabetic mice, but aggravates urinary albumin and immunoglobulin G content, possibly resulting from proximal tubule dysfunction.
[Mh] Termos MeSH primário: Albuminúria/tratamento farmacológico
Diabetes Mellitus Tipo 2/tratamento farmacológico
Nefropatias Diabéticas/prevenção & controle
Hipoglicemiantes/farmacologia
Cloreto de Lítio/farmacologia
[Mh] Termos MeSH secundário: Albuminúria/etiologia
Animais
Glicemia
Diabetes Mellitus Tipo 2/sangue
Diabetes Mellitus Tipo 2/complicações
Nefropatias Diabéticas/sangue
Avaliação Pré-Clínica de Medicamentos
Feminino
Quinase 3 da Glicogênio Sintase/metabolismo
Hipoglicemiantes/uso terapêutico
Rim/efeitos dos fármacos
Rim/enzimologia
Rim/patologia
Cloreto de Lítio/uso terapêutico
Camundongos Obesos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Hypoglycemic Agents); EC 2.7.11.26 (Glycogen Synthase Kinase 3); G4962QA067 (Lithium Chloride)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189485


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[PMID]:28621459
[Au] Autor:Hu L; Su P; Yin C; Zhang Y; Li R; Yan K; Chen Z; Li D; Zhang G; Wang L; Miao Z; Qian A; Xian CJ
[Ad] Endereço:Laboratory for Bone Metabolism, Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China.
[Ti] Título:Microtubule actin crosslinking factor 1 promotes osteoblast differentiation by promoting ß-catenin/TCF1/Runx2 signaling axis.
[So] Source:J Cell Physiol;233(2):1574-1584, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Osteoblast differentiation is a multistep process delicately regulated by many factors, including cytoskeletal dynamics and signaling pathways. Microtubule actin crosslinking factor 1 (MACF1), a key cytoskeletal linker, has been shown to play key roles in signal transduction and in diverse cellular processes; however, its role in regulating osteoblast differentiation is still needed to be elucidated. To further uncover the functions and mechanisms of action of MACF1 in osteoblast differentiation, we examined effects of MACF1 knockdown (MACF1-KD) in MC3T3-E1 osteoblastic cells on their osteoblast differentiation and associated molecular mechanisms. The results showed that knockdown of MACF1 significantly suppressed mineralization of MC3T3-E1 cells, down-regulated the expression of key osteogenic genes alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and type I collagen α1 (Col Iα1). Knockdown of MACF1 dramatically reduced the nuclear translocation of ß-catenin, decreased the transcriptional activation of T cell factor 1 (TCF1), and down-regulated the expression of TCF1, lymphoid enhancer-binding factor 1 (LEF1), and Runx2, a target gene of ß-catenin/TCF1. In addition, MACF1-KD increased the active level of glycogen synthase kinase-3ß (GSK-3ß), which is a key regulator for ß-catenin signal transduction. Moreover, the reduction of nuclear ß-catenin amount and decreased expression of TCF1 and Runx2 were significantly reversed in MACF1-KD cells when treated with lithium chloride, an agonist for ß-catenin by inhibiting GSK-3ß activity. Taken together, these findings suggest that knockdown of MACF1 in osteoblastic cells inhibits osteoblast differentiation through suppressing the ß-catenin/TCF1-Runx2 axis. Thus, a novel role of MACF1 in and a new mechanistic insight of osteoblast differentiation are uncovered.
[Mh] Termos MeSH primário: Diferenciação Celular
Fator 1-alfa Nuclear de Hepatócito/metabolismo
Proteínas dos Microfilamentos/metabolismo
Osteoblastos/metabolismo
Osteogênese
beta Catenina/metabolismo
[Mh] Termos MeSH secundário: Células 3T3
Animais
Diferenciação Celular/efeitos dos fármacos
Diferenciação Celular/genética
Subunidade alfa 1 de Fator de Ligação ao Core/genética
Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo
Regulação da Expressão Gênica
Glicogênio Sintase Quinase 3 beta/metabolismo
Fator 1-alfa Nuclear de Hepatócito/genética
Cloreto de Lítio/farmacologia
Camundongos
Proteínas dos Microfilamentos/genética
Osteoblastos/efeitos dos fármacos
Osteogênese/efeitos dos fármacos
Osteogênese/genética
Fenótipo
Fosforilação
Interferência de RNA
Transdução de Sinais
Fatores de Tempo
Transfecção
beta Catenina/agonistas
beta Catenina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CTNNB1 protein, mouse); 0 (Core Binding Factor Alpha 1 Subunit); 0 (Hepatocyte Nuclear Factor 1-alpha); 0 (Hnf1a protein, mouse); 0 (Macf1 protein, mouse); 0 (Microfilament Proteins); 0 (Runx2 protein, mouse); 0 (beta Catenin); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); EC 2.7.11.1 (Gsk3b protein, mouse); G4962QA067 (Lithium Chloride)
[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:170617
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.26059


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[PMID]:28383811
[Au] Autor:Huang CY; Lee FL; Peng SF; Lin KH; Chen RJ; Ho TJ; Tsai FJ; Padma VV; Kuo WW; Huang CY
[Ad] Endereço:Translation Research Core, China Medical University Hospital, China Medical University, Taichung, Taiwan.
[Ti] Título:HSF1 phosphorylation by ERK/GSK3 suppresses RNF126 to sustain IGF-IIR expression for hypertension-induced cardiomyocyte hypertrophy.
[So] Source:J Cell Physiol;233(2):979-989, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure (HF). Inhibition of extracellular signal-regulated kinases (ERK) efficaciously suppressed angiotensin II (ANG II)-induced cardiomyocyte hypertrophy and apoptosis by blocking insulin-like growth factor II receptor (IGF-IIR) signaling. However, the detailed mechanism by which ANG II induces ERK-mediated IGF-IIR signaling remains elusive. Here, we found that ANG II activated ERK to upregulate IGF-IIR expression via the angiotensin II type I receptor (AT R). ERK activation subsequently phosphorylates HSF1 at serine 307, leading to a secondary phosphorylation by glycogen synthase kinase III (GSK3) at serine 303. Moreover, we found that ANG II mediated ERK/GSK3-induced IGF-IIR protein stability by downregulating the E3 ubiquitin ligase of IGF-IIR RING finger protein CXXVI (RNF126). The expression of RNF126 decreased following ANG II-induced HSF1 phosphorylation, resulting in IGF-IIR protein stability and increased cardiomyocyte injury. Inhibition of GSK3 significantly alleviated ANG II-induced cardiac hypertrophy in vivo and in vitro. Taken together, these results suggest that HSF1 phosphorylation stabilizes IGF-IIR protein stability by downregulating RNF126 during cardiac hypertrophy. ANG II activates ERK/GSK3 to phosphorylate HSF1, resulting in RNF126 degradation, which stabilizes IGF-IIR protein expression and eventually results in cardiac hypertrophy. HSF1 could be a valuable therapeutic target for cardiac diseases among hypertensive patients.
[Mh] Termos MeSH primário: Cardiomegalia/etiologia
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Glicogênio Sintase Quinase 3 beta/metabolismo
Fatores de Transcrição de Choque Térmico/metabolismo
Proteínas de Choque Térmico/metabolismo
Hipertensão/complicações
Miócitos Cardíacos/enzimologia
Receptor IGF Tipo 2/metabolismo
Ubiquitina-Proteína Ligases/metabolismo
[Mh] Termos MeSH secundário: Angiotensina II/farmacologia
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia
Animais
Anti-Hipertensivos/farmacologia
Apoptose
Compostos de Bifenilo/farmacologia
Cardiomegalia/enzimologia
Cardiomegalia/patologia
Cardiomegalia/prevenção & controle
Linhagem Celular
Modelos Animais de Doenças
Relação Dose-Resposta a Droga
Feminino
Hipertensão/tratamento farmacológico
Hipertensão/enzimologia
Hipertensão/patologia
Cloreto de Lítio/farmacologia
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/patologia
Fosforilação
Estabilidade Proteica
Transporte Proteico
Ratos Endogâmicos SHR
Ratos Endogâmicos WKY
Receptor Tipo 1 de Angiotensina/metabolismo
Transdução de Sinais
Tetrazóis/farmacologia
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiotensin II Type 1 Receptor Blockers); 0 (Antihypertensive Agents); 0 (Biphenyl Compounds); 0 (Heat Shock Transcription Factors); 0 (Heat-Shock Proteins); 0 (Hsf1 protein, rat); 0 (Receptor, Angiotensin, Type 1); 0 (Receptor, IGF Type 2); 0 (Tetrazoles); 11128-99-7 (Angiotensin II); EC 2.3.2.27 (Rnf126 protein, rat); EC 2.3.2.27 (Ubiquitin-Protein Ligases); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); EC 2.7.11.1 (Gsk3b protein, rat); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); G4962QA067 (Lithium Chloride); J0E2756Z7N (irbesartan)
[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:170407
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25945


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[PMID]:28926590
[Au] Autor:Miyamoto K; Ohkawara B; Ito M; Masuda A; Hirakawa A; Sakai T; Hiraiwa H; Hamada T; Ishiguro N; Ohno K
[Ad] Endereço:Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
[Ti] Título:Fluoxetine ameliorates cartilage degradation in osteoarthritis by inhibiting Wnt/ß-catenin signaling.
[So] Source:PLoS One;12(9):e0184388, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Abnormal activation of the Wnt/ß-catenin signaling is implicated in the osteoarthritis (OA) pathology. We searched for a pre-approved drug that suppresses abnormally activated Wnt/ß-catenin signaling and has a potency to reduce joint pathology in OA. We introduced the TOPFlash reporter plasmid into HCS-2/8 human chondrosarcoma cells to estimate the Wnt/ß-catenin activity in the presence of 10 µM each compound in a panel of pre-approved drugs. We found that fluoxetine, an antidepressant in the class of selective serotonin reuptake inhibitors (SSRI), down-regulated Wnt/ß-catenin signaling in human chondrosarcoma cells. Fluoxetine inhibited both Wnt3A- and LiCl-induced loss of proteoglycans in chondrogenically differentiated ATDC5 cells. Fluoxetine increased expression of Sox9 (the chondrogenic master regulator), and decreased expressions of Axin2 (a marker for Wnt/ß-catenin signaling) and Mmp13 (matrix metalloproteinase 13). Fluoxetine suppressed a LiCl-induced increase of total ß-catenin and a LiCl-induced decrease of phosphorylated ß-catenin in a dose-dependent manner. An in vitro protein-binding assay showed that fluoxetine enhanced binding of ß-catenin with Axin1, which is a scaffold protein forming the degradation complex for ß-catenin. Fluoxetine suppressed LiCl-induced ß-catenin accumulation in human OA chondrocytes. Intraarticular injection of fluoxetine in a rat OA model ameliorated OA progression and suppressed ß-catenin accumulation.
[Mh] Termos MeSH primário: Cartilagem Articular/efeitos dos fármacos
Fluoxetina/farmacologia
Inibidores da Captação de Serotonina/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Proteína Axina/genética
Proteína Axina/metabolismo
Cartilagem Articular/metabolismo
Cartilagem Articular/patologia
Diferenciação Celular/efeitos dos fármacos
Células Cultivadas
Condrócitos/citologia
Condrócitos/efeitos dos fármacos
Condrócitos/metabolismo
Condrogênese/efeitos dos fármacos
Modelos Animais de Doenças
Regulação para Baixo/efeitos dos fármacos
Fluoxetina/uso terapêutico
Seres Humanos
Cloreto de Lítio/toxicidade
Metaloproteinase 13 da Matriz/genética
Metaloproteinase 13 da Matriz/metabolismo
Osteoartrite/tratamento farmacológico
Osteoartrite/metabolismo
Osteoartrite/patologia
Fosforilação/efeitos dos fármacos
Ratos
Ratos Sprague-Dawley
Fatores de Transcrição SOX9/genética
Fatores de Transcrição SOX9/metabolismo
Inibidores da Captação de Serotonina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AXIN2 protein, human); 0 (Axin Protein); 0 (SOX9 Transcription Factor); 0 (Serotonin Uptake Inhibitors); 01K63SUP8D (Fluoxetine); EC 3.4.24.- (Matrix Metalloproteinase 13); G4962QA067 (Lithium Chloride)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184388


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[PMID]:28911173
[Au] Autor:Bai L; Chang HM; Cheng JC; Chu G; Leung PCK; Yang G
[Ad] Endereço:College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, People's Republic of China.
[Ti] Título:Lithium Chloride Increases COX-2 Expression and PGE2 Production in a Human Granulosa-Lutein SVOG Cell Line Via a GSK-3ß/ß-Catenin Signaling Pathway.
[So] Source:Endocrinology;158(9):2813-2825, 2017 Sep 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lithium chloride (LiCl) is widely prescribed for the treatment of bipolar disorders and is associated with a higher incidence of reproductive adverse effects. Cyclooxygenase (COX)-2 and its derivative, prostaglandin E2 (PGE2), play regulatory roles in the human ovulatory process. Whether LiCl affects ovulation by regulating COX2 expression and PGE2 production in the human ovary is still largely unknown. The aim of this study was to investigate the effect of LiCl on the expression of COX-2 and production of PGE2 in human granulosa-lutein (hGL) cells, as well as the mechanisms underlying this effect. Both immortalized and primary hGL cells were used as research models. Using dual inhibition approaches, our results show that LiCl initiates the hGL cellular action by inhibiting the activity of glycogen synthase kinase-3ß [GSK-3ß (phosphorylation of GSK-3ß)] and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not by affecting protein kinase B or cAMP response element binding protein signaling. Additionally, the phosphorylation of GSK-3ß, but not ERK1/2, resulted in the stabilization and nuclear localization of ß-catenin. Furthermore, knockdown of either ß-catenin or GSK-3ß reversed the LiCl-induced upregulation of COX-2 expression. These results indicate that LiCl upregulates the expression of COX-2 and the subsequent production of PGE2 through the canonical GSK-3ß/ß-catenin signaling pathway in hGL cells.
[Mh] Termos MeSH primário: Ciclo-Oxigenase 2/genética
Dinoprostona/metabolismo
Cloreto de Lítio/farmacologia
Células Lúteas/efeitos dos fármacos
Células Lúteas/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular
Ciclo-Oxigenase 2/metabolismo
Feminino
Glicogênio Sintase Quinase 3 beta/metabolismo
Seres Humanos
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/genética
Regulação para Cima/efeitos dos fármacos
Regulação para Cima/genética
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (beta Catenin); EC 1.14.99.1 (Cyclooxygenase 2); EC 1.14.99.1 (PTGS2 protein, human); EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta); G4962QA067 (Lithium Chloride); K7Q1JQR04M (Dinoprostone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-00287


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[PMID]:28807209
[Au] Autor:Kan C; Liu A; Fang H; Dirsch O; Dahmen U; Boettcher M
[Ad] Endereço:Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Friedrich Schiller University of Jena, Jena, Germany; Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, China.
[Ti] Título:Induction of autophagy reduces ischemia/reperfusion injury in steatotic rat livers.
[So] Source:J Surg Res;216:207-218, 2017 Aug.
[Is] ISSN:1095-8673
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the reasons is an underlying impairment of autophagy. Autophagy is regulated by glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinases (ERK1/2) pathways. Both of them are target proteins of a cell-protective drug, lithium chloride. Lithium chloride treatment reduces IRI in many organs including liver. Therefore, we aimed to investigate the effect of lithium chloride treatment on autophagy induction in steatotic rat livers. We also wanted to evaluate the related cell-protective effects on the enhanced hepatic IRI. MATERIALS AND METHODS: After inducing hepatic steatosis, rats were injected with lithium chloride or normal saline for 3 d before being subjected to 70% selective warm ischemia for 60 min. After reperfusion, rats were observed for 30 min, 6, 24, and 48 h. RESULTS: Lithium chloride appeared to protect hepatocytes from IRI via its ability to induce autophagy by modulation of both GSK3b and ERK1/2 pathways. Hepatic damage was significantly decreased in the treatment group as indicated by a reduced inflammatory response, less apoptosis, less necrosis, and lower liver enzyme levels. CONCLUSIONS: Simultaneous modulation of GSK3b and ERK1/2 pathways might be an interesting strategy to reduce IRI in steatotic livers with an impairment of autophagy.
[Mh] Termos MeSH primário: Autofagia/efeitos dos fármacos
Fígado Gorduroso/complicações
Cloreto de Lítio/uso terapêutico
Fígado/efeitos dos fármacos
Substâncias Protetoras/uso terapêutico
Traumatismo por Reperfusão/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Autofagia/fisiologia
Biomarcadores/metabolismo
Hepatócitos/efeitos dos fármacos
Hepatócitos/metabolismo
Hepatócitos/patologia
Cloreto de Lítio/farmacologia
Fígado/irrigação sanguínea
Fígado/metabolismo
Fígado/patologia
Masculino
Substâncias Protetoras/farmacologia
Ratos
Ratos Endogâmicos Lew
Traumatismo por Reperfusão/complicações
Traumatismo por Reperfusão/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Protective Agents); G4962QA067 (Lithium Chloride)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170816
[St] Status:MEDLINE



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