Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biochem Biophys Res Commun ; 710: 149887, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38581954

RESUMO

SS-31 is a mitochondria-targeting short peptide. Recent studies have indicated its hepatoprotective effects. In our study, we investigated the impact of SS-31 on LPS-induced autophagy in HepG2 cells. The results obtained from a dual-fluorescence autophagy detection system revealed that SS-31 promotes the formation of autolysosomes and autophagosomes, thereby facilitating autophagic flux to a certain degree. Additionally, both ELISA and qPCR analyses provided further evidence that SS-31 safeguards HepG2 cells against inflammatory responses triggered by LPS through ATG5-dependent autophagy. In summary, our study demonstrates that SS-31 inhibits LPS-stimulated inflammation in HepG2 cells by upregulating ATG5-dependent autophagy.


Assuntos
Autofagia , Lipopolissacarídeos , Humanos , Células Hep G2 , Lipopolissacarídeos/farmacologia , Autofagossomos , Inflamação , Proteína 5 Relacionada à Autofagia/genética
2.
Life Sci ; 277: 119490, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33862114

RESUMO

AIMS: Sepsis-associated encephalopathy (SAE) is one of the most common complications of sepsis, and it might lead to long-term cognitive dysfunction and disability. This study aimed to explore the role of S100 calcium binding protein B (S100B)/RAGE/ceramide signaling pathway in SAE. MAIN METHODS: FPS-ZM1 (an inhibitor of RAGE), myriocin and GW4869 (an inhibitor of ceramide) were used to explore the role of S100B/RAGE/ceramide in acute brain injury and long-term cognitive impairment in sepsis. In addition, Mdivi-1 (inhibitor of Drp1) and Drp1 siRNA were utilized to assess the effects of C2-ceramide on neuronal mitochondria, and to explore the specific underlying mechanism in C2 ceramide-induced death of HT22 mouse hippocampal neuronal cells. KEY FINDINGS: Western blot analysis showed that sepsis significantly up-regulated S100B and RAGE. Nissl staining and Morris water maze (MWM) test revealed that inhibition of RAGE with FPS-ZM1 markedly attenuated cecal ligation and puncture (CLP)-induced brain damage and cognitive dysfunction. Furthermore, FPS-ZM1 relieved sepsis-induced C2-ceramide accumulation and abnormal mitochondrial dynamics. Moreover, inhibition of ceramide also showed similar protective effects both in vivo and in vitro. Furthermore, Mdivi-1 and Drp1 siRNA significantly reduced C2-ceramide-induced neuronal mitochondrial fragmentation and cell apoptosis in vitro. SIGNIFICANCE: This study confirmed that S100B regulates mitochondrial dynamics through RAGE/ceramide pathway, in addition to the role of this pathway in acute brain injury and long-term cognitive impairment during sepsis.


Assuntos
Ceramidas/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encefalopatias/complicações , Encefalopatias/metabolismo , Lesões Encefálicas/metabolismo , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Sepse/complicações , Encefalopatia Associada a Sepse/complicações , Encefalopatia Associada a Sepse/fisiopatologia , Transdução de Sinais
3.
Metab Brain Dis ; 36(4): 601-608, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33475982

RESUMO

Micro-RNA125b (miR-125b) and tumor protein p53 (p53) are involved in the regulation of mitochondrial dynamics; however, the mechanism of their possible interaction during oxidative stress remains unclear. In this study, we investigated the role and mechanism of miR-125b and p53 in oxidative stress-induced mitochondrial damage in immortalized mouse hippocampal HT22 cells. Following stimulation with H2O2, we observed downregulation of miR-125b expression, upregulation of p53 expression, mitochondria were damaged and increased cell death. Overexpression of miR-125b alleviated mitochondrial damage and inhibited p53 expression. Furthermore, confocal and electron microscopy showed that overexpression of p53 eliminated the protective effect of miR-125b on the mitochondria. Thus, miR-125b alleviates abnormal mitochondrial homeostasis in H2O2-treated HT22 cells by suppressing p53 expression. Our data reveal a new model by which miR-125b influences mitochondrial dynamics.


Assuntos
Peróxido de Hidrogênio/toxicidade , MicroRNAs/biossíntese , Dinâmica Mitocondrial/fisiologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Transformada , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Camundongos , MicroRNAs/genética , Dinâmica Mitocondrial/efeitos dos fármacos
4.
J Mol Neurosci ; 70(12): 2049-2057, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32468218

RESUMO

Sepsis can induce acute and chronic changes in the central nervous system termed sepsis-associated encephalopathy (SAE). Not only cognitive deficits but also anxiety, depression, and post-traumatic stress disorder are common in severe sepsis survivors. In this study, we demonstrated that amitriptyline, a classic tricyclic antidepressant, reduced sepsis-induced brain damage through the tropomyosin receptor kinase A (TrkA) signaling pathway. Amitriptyline ameliorated neuronal loss assessed by Nissl staining in a mouse cecal ligation and puncture (CLP)-induced sepsis model. Furthermore, amitriptyline reduced early gliosis assessed by immunofluorescence and late cognitive deficits assessed by the Morris water maze (MWM) test. Moreover, amitriptyline treatment attenuated oxidative stress indicated by less superoxide dismutase (SOD) and catalase (CAT) activity consumption and malondialdehyde (MDA) accumulation. Interestingly, those protective effects of amitriptyline could be abolished by GW441756, a TrkA signaling pathway inhibitor. Immunoblot directly showed that TrkA signaling pathway-associated proteins, such as Akt and GSK3ß, were involved in the neuroprotective effects of amitriptyline. Thus, amitriptyline appears to be an encouraging candidate to treat cognitive deficits and depression after severe sepsis.


Assuntos
Amitriptilina/farmacologia , Antidepressivos Tricíclicos/farmacologia , Receptor trkA/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Transdução de Sinais , Amitriptilina/uso terapêutico , Animais , Antidepressivos Tricíclicos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Gliose/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Indóis/farmacologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Superóxido Dismutase/metabolismo
5.
Pulm Pharmacol Ther ; 62: 101918, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251714

RESUMO

Sepsis is among the most devastating events in intensive care units. As a complication of sepsis, acute lung injury (ALI) is common and highly associated with poor outcome. The present study demonstrated that abnormal mitochondrial dynamics play a pivotal role in lipopolysaccharide (LPS)-induced ALI. Inhibiting the mitochondrial fission with the specific inhibitor-1 (Mdivi-1) ameliorated ALI as assessed by hematoxylin and eosin (H&E) staining and wet/dry ratio. Furthermore, Mdivi-1 reduced mitogen-activated protein kinases (MAPKs) activation, oxidative stress and apoptosis in the lungs. Plasma pro-inflammation cytokines were also reduced significantly in Mdivi-1-treated mice. In vitro study revealed that Mdivi-1 protected the macrophages from LPS-induced MAPKs activation, oxidative stress and cell apoptosis. Mdivi-1 also inhibited the release of pro-inflammatory cytokines. Morphological analysis showed that Mdivi-1 rescued the macrophages from LPS-induced mitochondrial fragmentation. Moreover, LPS treatment induced significant phosphorylation of Drp1 at Ser616, dephosphorylation at Ser637 and translocation of Drp1 from the cytoplasm to mitochondria, while Mdivi-1 inhibited those effects. Thus, modification of fission to rebuild mitochondrial homeostasis may offer an innovative opportunity for developing therapeutic strategies against ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quinazolinonas/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Citocinas/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Modelos Animais , Células RAW 264.7
6.
Biochem Biophys Res Commun ; 520(1): 171-178, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31582222

RESUMO

SS-31 is a kind of mitochondrion-targeted peptide. Recent studies indicated significant neuroprotective effects of SS-31. In this study, we investigated that SS-31 protected the murine cultured microglial cells (BV-2) against lipopolysaccharide (LPS)-induced inflammation and oxidative stress through stabilizing mitochondrial morphology. The morphological study showed that SS-31 preserved LPS-induced mitochondrial ultrastructure by reducing the fission protein 1 (Fis1) expression. Flow cytometry and Western blot verified that SS-31 defended the BV-2 cells against LPS-stimulated inflammation and oxidative stress via suppressing Fis1. To sum up, our study represents that SS-31 preserves BV-2 cells from LPS-stimulated inflammation and oxidative stress by down-regulating the Fis1 expression.


Assuntos
Inflamação , Lipopolissacarídeos/metabolismo , Microglia/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Oligopeptídeos/farmacologia , Estresse Oxidativo , Animais , Lentivirus/metabolismo , Camundongos , Microglia/metabolismo , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , RNA Interferente Pequeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...