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[PMID]:29203747
[Au] Autor:Mielczarek-Puta M; Chrzanowska A; Otto-Slusarczyk D; Grabon W; Baranczyk-Kuzma A
[Ad] Endereço:Katedra I Zaklad Biochemii, Warszawski Uniwersytet Medyczny, Warszawa, Polska.
[Ti] Título:[Effect of antioxidants on human primary and metastatic colon cancer cells at hypoxia and normoxia].
[So] Source:Wiad Lek;70(5):946-952, 2017.
[Is] ISSN:0043-5147
[Cp] País de publicação:Poland
[La] Idioma:pol
[Ab] Resumo:THE AIM: Evaluation of some antioxidants on human colon cancer cells viability and proliferation at various oxygen levels. MATERIAL AND METHODS: Human primary (SW480) and metastatic (SW620) colon cancer cells were cultured at hypoxia (1% oxygen), tissues (10% oxygen) and atmospheric (21% oxygen) normoxia with quercetin, epigallocatechin gallate, lipoic acid, hydroxycitric acid, their mixture, and without studied compounds (control). Antioxidants were used at physiological concentrations. The cell viability was determined by trypan blue dye exclusion and proliferation by MTT assay. RESULTS: The viability of each line ranged from 80% to 97%, and it was independent on the compound and oxygen availability. At hypoxia the cell count of both lines was lower than for the controls in the presence of each studied compound. At tissue normoxia the cell count of primary cancer cells was decreased only with epigallocatechin gallate, whereas metastatic cells were sensitive for each antioxidant. CONCLUSIONS: Our results indicated, that the studied antioxidants were not cytotoxic at physiological levels for both pirmary and metastatic colon cancer. Their cytostatic effect depend on the type of cell, oxygen availability and antioxidant concentration.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Hipóxia Celular/efeitos dos fármacos
Neoplasias do Colo/tratamento farmacológico
[Mh] Termos MeSH secundário: Catequina/análogos & derivados
Catequina/farmacologia
Linhagem Celular Tumoral/efeitos dos fármacos
Citratos/farmacologia
Neoplasias do Colo/patologia
Seres Humanos
Metástase Neoplásica
Oxigênio/farmacologia
Ácido Tióctico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Citrates); 73Y7P0K73Y (Thioctic Acid); 8R1V1STN48 (Catechin); 8W94T9026R (hydroxycitric acid); BQM438CTEL (epigallocatechin gallate); S88TT14065 (Oxygen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE


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[PMID]:28470667
[Au] Autor:Tanaka T; Zhang W; Sun Y; Shuai Z; Chida AS; Kenny TP; Yang GX; Sanz I; Ansari A; Bowlus CL; Ippolito GC; Coppel RL; Okazaki K; He XS; Leung PSC; Gershwin ME
[Ad] Endereço:Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA.
[Ti] Título:Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics.
[So] Source:Hepatology;66(3):885-895, 2017 09.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A major problem in autoimmunity has been identification of the earliest events that lead to breach of tolerance. Although there have been major advances in dissecting effector pathways and the multilineage immune responses to mitochondrial self-antigens in primary biliary cholangitis, the critical links between environmental factors and tolerance remain elusive. We hypothesized that environmental xenobiotic modification of the E2 subunit of the pyruvate dehydrogenase (PDC-E2) inner lipoyl domain can lead to loss of tolerance to genetically susceptible hosts. Previously we demonstrated that serum anti-PDC-E2 autoantibodies cross-react with the chemical xenobiotics 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid and further that there is a high frequency of PDC-E2-specific peripheral plasmablasts. Herein we generated 104 recombinant monoclonal antibodies (mAbs) based on paired heavy-chain and light-chain variable regions of individual plasmablasts derived from primary biliary cholangitis patients. We identified 32 mAbs reactive with native PDC-E2, including 20 specific for PDC-E2 and 12 cross-reactive with both PDC-E2 and 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid. A lower frequency of replacement somatic hypermutations, indicating a lower level of affinity maturation, was observed in the complementarity-determining regions of the cross-reactive mAbs in comparison to mAbs exclusively recognizing PDC-E2 or those for irrelevant antigens. In particular, when the highly mutated heavy-chain gene of a cross-reactive mAb was reverted to the germline sequence, the PDC-E2 reactivity was reduced dramatically, whereas the xenobiotic reactivity was retained. Importantly, cross-reactive mAbs also recognized lipoic acid, a mitochondrial fatty acid that is covalently bound to PDC-E2. CONCLUSION: Our data reflect that chemically modified lipoic acid or lipoic acid itself, through molecular mimicry, is the initial target that leads to the development of primary biliary cholangitis. (Hepatology 2017;66:885-895).
[Mh] Termos MeSH primário: Anticorpos Monoclonais/imunologia
Autoantígenos/imunologia
Autoimunidade/genética
Colangite/imunologia
Colangite/patologia
Xenobióticos/imunologia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/metabolismo
Autoantígenos/genética
Autoimunidade/imunologia
Feminino
Amplificação de Genes
Seres Humanos
Immunoblotting
Masculino
Mimetismo Molecular/genética
Reação em Cadeia da Polimerase em Tempo Real
Sensibilidade e Especificidade
Ácido Tióctico/imunologia
Ácido Tióctico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Autoantigens); 0 (Xenobiotics); 73Y7P0K73Y (Thioctic Acid)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1002/hep.29245


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[PMID]:29334926
[Au] Autor:Ghelani H; Razmovski-Naumovski V; Pragada RR; Nammi S
[Ad] Endereço:School of Science and Health, Western Sydney University, Sydney, NSW, 2751, Australia.
[Ti] Título:(R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.
[So] Source:BMC Complement Altern Med;18(1):13, 2018 Jan 15.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. RESULTS: The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. CONCLUSION: These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.
[Mh] Termos MeSH primário: Frutose/metabolismo
Produtos Finais de Glicação Avançada/metabolismo
Glicosilação/efeitos dos fármacos
Mioglobina/metabolismo
Ácido Tióctico/farmacologia
[Mh] Termos MeSH secundário: Animais
Produtos Finais de Glicação Avançada/análise
Mioglobina/análise
Mioglobina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycation End Products, Advanced); 0 (Myoglobin); 30237-26-4 (Fructose); 73Y7P0K73Y (Thioctic Acid)
[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:180117
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-2076-6


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[PMID]:29419686
[Au] Autor:Wang X; Lin H; Xu S; Jin Y; Zhang R
[Ad] Endereço:Shenzhen Bao'an Traditional Chinese Medicine Hospital Group, Guangzhou University of Chinese Medicine, Shenzhen.
[Ti] Título:The clinical efficacy of epalrestat combined with α-lipoic acid in diabetic peripheral neuropathy: Protocol for a systematic review and meta-analysis.
[So] Source:Medicine (Baltimore);97(6):e9828, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus, affecting patients in the world. Epalrestat combined with α-lipoic acid (ALA) is the most frequent combine therapy used in the DPN researches. We aim to assess the effectiveness and safety of epalrestat combined with ALA in patients with DPN, compare with epalrestat alone. METHODS: We will search Cochrane Library, PubMed, Wanfang Data, China National Knowledge Infrastructure, VIP Chinese Science and Technology Journals Database, and Chinese Biomedical Database from inception until October 31th, 2017. Inclusion the randomized controlled trials and clinical control trials of combine therapy which evaluate clinical efficacy and side effect in people with DPN. Data extraction and risk of bias assessments will be independently conducted by 2 reviewers. The primary outcome measures will be total effective rate, motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), Toronto clinical scoring system (TCSS), and total symptom score (TSS). All statistical analyses will be performed using RevMan V.5.3 software. RESULTS: This review will evaluate the total effective rate, nerve conduction velocity, TCSS, TSS, and safety of ALA combined with epalrestat for patients with DPN, compare with epalrestat alone. CONCLUSION: Our study will provide evidence to assess whether epalrestat combined with ALA is an optional treatment for patients with DPN.
[Mh] Termos MeSH primário: Neuropatias Diabéticas/tratamento farmacológico
Metanálise como Assunto
Rodanina/análogos & derivados
Tiazolidinas
Ácido Tióctico
[Mh] Termos MeSH secundário: Antioxidantes/administração & dosagem
Antioxidantes/efeitos adversos
Quimioterapia Combinada
Inibidores Enzimáticos/administração & dosagem
Inibidores Enzimáticos/efeitos adversos
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
Projetos de Pesquisa
Rodanina/administração & dosagem
Rodanina/efeitos adversos
Tiazolidinas/administração & dosagem
Tiazolidinas/efeitos adversos
Ácido Tióctico/administração & dosagem
Ácido Tióctico/efeitos adversos
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Enzyme Inhibitors); 0 (Thiazolidines); 424DV0807X (epalrestat); 73Y7P0K73Y (Thioctic Acid); 7O50LKL2G8 (Rhodanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180209
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009828


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[PMID]:29025653
[Au] Autor:Yang S; Wang Y; Ren Z; Chen M; Chen W; Zhang X
[Ad] Endereço:Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
[Ti] Título:Stepwise pH/reduction-responsive polymeric conjugates for enhanced drug delivery to tumor.
[So] Source:Mater Sci Eng C Mater Biol Appl;82:234-243, 2018 Jan 01.
[Is] ISSN:1873-0191
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In this research, a charge-conversional polymer, poly-l-lysine-lipoic acid (PLL-LA), was prepared by dimethylmaleic anhydride (DA) modification and applied as a carrier with enhanced cell internalization and intracellular pH- and reduction-triggered doxorubicin (Dox) release. The surface charge of dimethylmaleic anhydride-poly-l-lysine-lipoic acid micelles (DA-PLL-LA) was negative at physiological pH and reversed to positive at the extracellular and intracellular pH of cancer cells. At tumor extracellular pH of 6.8, the conjugates underwent a rapid charge-reversible process with almost 80% DA cleavage within 2h, and then endocytosed into the endo/lysosomes more rapidly than at physiological pH of 7.4. The Dox/DA-PLL-LA micelles (Dox-micelles) demonstrated a sustained drug release in vitro under physiological condition, and rapid Dox release was triggered by both extracellular pH and high-concentration reducing glutathione. The Dox-micelles also exhibited enhanced internalization at extracellular pH, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Excellent tumor-penetrating efficacy was also found in A549 tumor spheroids and solid tumor slices. Moreover, the DA-PLL-LA micelles exhibited excellent tumor-targeting ability in tumor tissues and excellent antitumor efficacy and low systemic toxicity in breast tumor-bearing mice. Therefore, the DA-PLL-LA micelles demonstrated great potential for targeted and efficient drug delivery in cancer treatments.
[Mh] Termos MeSH primário: Antibióticos Antineoplásicos/química
Doxorrubicina/química
Portadores de Fármacos/química
Polímeros/química
[Mh] Termos MeSH secundário: Células A549
Animais
Antibióticos Antineoplásicos/uso terapêutico
Antibióticos Antineoplásicos/toxicidade
Sobrevivência Celular/efeitos dos fármacos
Doxorrubicina/uso terapêutico
Doxorrubicina/toxicidade
Portadores de Fármacos/síntese química
Liberação Controlada de Fármacos
Seres Humanos
Concentração de Íons de Hidrogênio
Camundongos
Camundongos Endogâmicos BALB C
Micelas
Microscopia Confocal
Neoplasias/tratamento farmacológico
Neoplasias/patologia
Oxirredução
Fagocitose/efeitos dos fármacos
Polilisina/química
Polímeros/síntese química
Ácido Tióctico/química
Transplante Heterólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibiotics, Antineoplastic); 0 (Drug Carriers); 0 (Micelles); 0 (Polymers); 25104-18-1 (Polylysine); 73Y7P0K73Y (Thioctic Acid); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180205
[Lr] Data última revisão:
180205
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE


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[PMID]:28993193
[Au] Autor:Yang L; Wen Y; Lv G; Lin Y; Tang J; Lu J; Zhang M; Liu W; Sun X
[Ad] Endereço:Shenzhen Tumor Immuno-gene Therapy Clinical Application Engineering Lab, Biobank of Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, PR China; Institute of Immunology of Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510060, G
[Ti] Título:α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation.
[So] Source:Biochem Biophys Res Commun;494(1-2):325-331, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alpha lipoic acid (α -LA) is a naturally occurring antioxidant and metabolic enzyme co-factor. Recently, α -LA has been reported to inhibit the growth of various cancer cells, but the precise signaling pathways that mediate the effects of α -LA on non-small cell lung cancer (NSCLC) development remain unclear. METHODS: The CCK-8 assay was used to assess cell proliferation in NSCLC cell lines after α -LA treatment. The expression of growth factor receptor-bound protein 2 (Grb2), cyclin-dependent kinase (CDK)-2, CDK4, CDK6, Cyclin D3, Cyclin E1, Ras, c-Raf, epidermal growth factor receptor (EGFR), ERK1/2 and activated EGFR and ERK1/2 was evaluated by western blotting. Grb2 levels were restored in α-LA-treated cells by transfection of a plasmid carrying Grb2 and were reduced in NSCLC cells via specific siRNA-mediated knockdown. RESULTS: α -LA dramatically decreased NSCLC cell proliferation by downregulating Grb2; in contrast, Grb2 overexpression significantly prevented α-LA-induced decrease in cell growth in vitro. Western blot analysis indicated that α-LA decreased the levels of phospho-EGFR, CDK2/4/6, Cyclins D3 and E1, which are associated with the inhibition of G1/S-phase transition. Additional experiments indicated that Grb2 inhibition partially abolished EGF-induced phospho-EGFR and phospho-ERK1/2 activity. In addition, α-LA exerted greater inhibitory effects than gefitinib on NSCLC cells by preventing EGF-induced EGFR activation. CONCLUSION: For the first time, these findings provide the first evidence that α-LA inhibits cell proliferation through Grb2 by suppressing EGFR phosphorylation and that MAPK/ERK is involved in this pathway.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos
Proteína Adaptadora GRB2/antagonistas & inibidores
Regulação Neoplásica da Expressão Gênica
Ácido Tióctico/farmacologia
[Mh] Termos MeSH secundário: Células A549
Proliferação Celular/efeitos dos fármacos
Ciclina D3/genética
Ciclina D3/metabolismo
Ciclina E/genética
Ciclina E/metabolismo
Quinase 2 Dependente de Ciclina/genética
Quinase 2 Dependente de Ciclina/metabolismo
Quinase 4 Dependente de Ciclina/genética
Quinase 4 Dependente de Ciclina/metabolismo
Quinase 6 Dependente de Ciclina/genética
Quinase 6 Dependente de Ciclina/metabolismo
Proteína Adaptadora GRB2/genética
Proteína Adaptadora GRB2/metabolismo
Seres Humanos
Proteína Quinase 1 Ativada por Mitógeno/genética
Proteína Quinase 1 Ativada por Mitógeno/metabolismo
Proteína Quinase 3 Ativada por Mitógeno/genética
Proteína Quinase 3 Ativada por Mitógeno/metabolismo
Proteínas Oncogênicas/genética
Proteínas Oncogênicas/metabolismo
Fosforilação/efeitos dos fármacos
Proteínas Proto-Oncogênicas c-raf/genética
Proteínas Proto-Oncogênicas c-raf/metabolismo
RNA Interferente Pequeno/genética
RNA Interferente Pequeno/metabolismo
Receptor do Fator de Crescimento Epidérmico/genética
Receptor do Fator de Crescimento Epidérmico/metabolismo
Transdução de Sinais
Proteínas ras/genética
Proteínas ras/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (CCND3 protein, human); 0 (CCNE1 protein, human); 0 (Cyclin D3); 0 (Cyclin E); 0 (GRB2 Adaptor Protein); 0 (GRB2 protein, human); 0 (Oncogene Proteins); 0 (RNA, Small Interfering); 73Y7P0K73Y (Thioctic Acid); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.11.1 (Proto-Oncogene Proteins c-raf); EC 2.7.11.22 (CDK2 protein, human); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (CDK6 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 2); EC 2.7.11.22 (Cyclin-Dependent Kinase 4); EC 2.7.11.22 (Cyclin-Dependent Kinase 6); EC 2.7.11.24 (MAPK1 protein, human); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1); EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3); EC 3.6.5.2 (ras Proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE


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[PMID]:28757203
[Au] Autor:Habarou F; Hamel Y; Haack TB; Feichtinger RG; Lebigot E; Marquardt I; Busiah K; Laroche C; Madrange M; Grisel C; Pontoizeau C; Eisermann M; Boutron A; Chrétien D; Chadefaux-Vekemans B; Barouki R; Bole-Feysot C; Nitschke P; Goudin N; Boddaert N; Nemazanyy I; Delahodde A; Kölker S; Rodenburg RJ; Korenke GC; Meitinger T; Strom TM; Prokisch H; Rotig A; Ottolenghi C; Mayr JA; de Lonlay P
[Ad] Endereço:Reference Center of Inherited Metabolic Diseases, University Paris Descartes, Hospital Necker Enfants Malades, APHP, 75015 Paris, France; Metabolic Biochemistry, University Paris Descartes, Hospital Necker Enfants Malades, 75015 Paris, France.
[Ti] Título:Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.
[So] Source:Am J Hum Genet;101(2):283-290, 2017 Aug 03.
[Is] ISSN:1537-6605
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2.
[Mh] Termos MeSH primário: Aciltransferases/genética
Atrofia/patologia
Encefalopatias/genética
Encéfalo/patologia
Lipoilação/genética
Mitocôndrias/metabolismo
[Mh] Termos MeSH secundário: Aminoácidos/metabolismo
Encéfalo/diagnóstico por imagem
Encefalopatias/patologia
Mapeamento Encefálico/métodos
Células Cultivadas
Metabolismo Energético/genética
Metabolismo Energético/fisiologia
Glicina/sangue
Seres Humanos
Recém-Nascido
Imagem por Ressonância Magnética
Mitocôndrias/genética
Consumo de Oxigênio/genética
Ligação Proteica/genética
Ácido Tióctico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 73Y7P0K73Y (Thioctic Acid); EC 2.3.- (Acyltransferases); EC 2.3.1.- (lipoyltransferase II); TE7660XO1C (Glycine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE


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[PMID]:28628643
[Au] Autor:Bernardinelli E; Costa R; Scantamburlo G; To J; Morabito R; Nofziger C; Doerrier C; Krumschnabel G; Paulmichl M; Dossena S
[Ad] Endereço:Institute of Pharmacology and Toxicology, Paracelsus Medical University, Salzburg, Austria.
[Ti] Título:Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.
[So] Source:PLoS One;12(6):e0179591, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lipoyl(Octanoyl) Transferase 2 (LIPT2) is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD) current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell), mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.
[Mh] Termos MeSH primário: Aciltransferases/metabolismo
Apoptose
Mitocôndrias/metabolismo
[Mh] Termos MeSH secundário: Aciltransferases/antagonistas & inibidores
Aciltransferases/genética
Apoptose/efeitos dos fármacos
Calreticulina/metabolismo
Caspase 3/metabolismo
Cloretos/metabolismo
Fragmentação do DNA/efeitos dos fármacos
Células HEK293
Células HeLa
Seres Humanos
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Microscopia Confocal
Técnicas de Patch-Clamp
Plasmídeos/genética
Plasmídeos/metabolismo
Interferência de RNA
RNA Interferente Pequeno/metabolismo
Estaurosporina/farmacologia
Ácido Tióctico/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calreticulin); 0 (Chlorides); 0 (RNA, Small Interfering); 73Y7P0K73Y (Thioctic Acid); EC 2.3.- (Acyltransferases); EC 2.3.1.- (lipoyltransferase II); EC 3.4.22.- (Caspase 3); H88EPA0A3N (Staurosporine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179591


  9 / 3326 MEDLINE  
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[PMID]:28602729
[Au] Autor:Wang Y; Everaert N; Song Z; Decuypere E; Vermeulen D; Buyse J
[Ad] Endereço:Laboratory of Livestock Physiology, Department of Biosystems, KU Leuven, Kasteelpark Arenberg 30, 3001 Leuven, Belgium.
[Ti] Título:Alpha-lipoic acid impairs body weight gain of young broiler chicks via modulating peripheral AMPK.
[So] Source:Comp Biochem Physiol A Mol Integr Physiol;211:34-40, 2017 Sep.
[Is] ISSN:1531-4332
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In mammals, the AMP-activated protein kinase (AMPK) pathways in the central and peripheral tissues coordinately integrate inputs from multiple sources to regulate energy balance. The present study was aimed to explore the potential role of hepatic AMPK in the energy homeostasis of broiler chickens. Diets with 0, 0.05% or 0.1% alpha-lipoic acid (α-LA), a known AMPK inhibitor were provided to broiler chicks for 7days. As a result, α-LA supplementation decreased the relative growth rate of broiler chicks. Hepatic AMPKα2 mRNA levels were significantly upregulated by dietary α-LA, in concert with the increased phosphorylated AMPKα protein levels. In addition, hepatic FAS mRNA levels together with the malonyl-CoA to total CoA ester ratio were reduced by α-LA supplementation. Moreover, the hepatic phosphorylated glycogen synthase levels were increased resulting in a markedly decreased hepatic glycogen content. In conclusion, dietary α-LA supplementation decreased the in vivo hepatic glycogenesis and lipogenesis via stimulating hepatic AMPKα mRNA levels and the phosphorylated gene product. The stimulatory effect of α-LA on hepatic AMPK mRNA and pAMPKα protein levels together with our previous observations regarding its inhibitory effect on hypothalamic AMPK may have altered the energy balance and hence impaired body weight gain of broiler chicks.
[Mh] Termos MeSH primário: Proteínas Quinases Ativadas por AMP/metabolismo
Galinhas/crescimento & desenvolvimento
Ácido Tióctico/farmacologia
Ganho de Peso/efeitos dos fármacos
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/antagonistas & inibidores
Proteínas Quinases Ativadas por AMP/genética
Animais
Masculino
Análise de Componente Principal
Inibidores de Proteínas Quinases/farmacologia
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 0 (RNA, Messenger); 73Y7P0K73Y (Thioctic Acid); EC 2.7.11.31 (AMP-Activated Protein Kinases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE


  10 / 3326 MEDLINE  
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[PMID]:28551626
[Au] Autor:Kuban-Jankowska A; Gorska-Ponikowska M; Wozniak M
[Ad] Endereço:Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland alicjakuban@gumed.edu.pl.
[Ti] Título:Lipoic Acid Decreases the Viability of Breast Cancer Cells and Activity of PTP1B and SHP2.
[So] Source:Anticancer Res;37(6):2893-2898, 2017 06.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. MATERIALS AND METHODS: We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases. RESULTS: ALA and DHLA decrease the activity of PTP1B and SHP2, and have inhibitory effects on the viability and proliferation of breast cancer cells. CONCLUSION: ALA and DHLA can be considered as potential agents for the adjunctive treatment of breast cancer.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Antioxidantes/farmacologia
Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo
Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo
Ácido Tióctico/farmacologia
[Mh] Termos MeSH secundário: Neoplasias da Mama
Sobrevivência Celular/efeitos dos fármacos
Seres Humanos
Antígenos Comuns de Leucócito/metabolismo
Células MCF-7
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antioxidants); 73Y7P0K73Y (Thioctic Acid); EC 3.1.3.48 (Leukocyte Common Antigens); EC 3.1.3.48 (PTPN1 protein, human); EC 3.1.3.48 (PTPRC protein, human); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1); EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE



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