Diazoxide protects against methylmalonate-induced neuronal toxicity

Kowaltowski, Alicia J.; Maciel, Evelise N.; Fornazari, Maynara; Castilho, Roger F.

doi:10.1016/j.expneurol.2006.04.004

Cited by 26 publications

(39 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Alguns estudos anteriores mostraram que agonistas de K ATP como cromakalina e DZX protegiam cérebro contra danos em isquemia/reperfusão (Heurteaux et al, 1993;Reshef et al, 1998;Domoki et al, 1999) Shimizu et al, 2002;Lenzser et al, 2005;Nakagawa et al, 2005). Nós demonstramos que a morte neuronal promovida por acidose metilmalônica, que ocorre por mecanismos similares aos encontrados em isquemia/reperfusão, podem ser prevenidos pela ativação de mitoK ATP , bem como pela inibição de transição de permeabilidade mitotondrial (TPM) (Kowaltowski et al, 2006).…”

Section: Fluxo De K + E Canais De K + Mitocondriais Sensíveis a Atpunclassified

“…Estes dados não corroboram com experimentos feitos pelo grupo (Kowaltowski et al, 2006) em células neuronais PC12 e fatias cerebrais. Nessas condições, diazóxido previne contra danos provocados por MMA.…”

Section: Não Foi Observada Nenhuma Redução Nos Danos Causados Por Mmaunclassified

“…Sem a enzima, metilmalonato se acumula nos tecidos e leva a danos celulares, principalmente em cérebro, já que o cérebro tem uma grande dependência pelo metabolismo aeróbico (Hoffmann et al, 1993;Hoffmann et al, 1994;Baulny et al, 2005). Acredita-se que estes danos cerebrais são devido a uma deficiência do metabolismo energético, semelhantes a condições isquêmicas (Brusque et al, 2002) promovidas pela ação inibitória de metilmalonato sobre o metabolismo de succinato (Maciel et al, 2004;Kowaltowski et al, 2006). Assim, estudos mitocondriais podem auxiliar em mecanismos para prevenir contra danos neuronais em caso de acidose por MMA.…”

Section: Estudo Da Permeabilização Mitocondrial Induzida Por Ca 2+ Emunclassified

“…Foi demonstrado que o MMA promove neurodegeneração de modo prevenido por diazóxido, em células PC12 e fatias cerebrais (Kowaltowski et al, 2006). Desta forma, realizamos experimentos para verificar se a abertura de mitoK ATP poderia inibir …”

Section: Estudo Da Permeabilização Mitocondrial Induzida Por Ca 2+ Emunclassified

“…Isso sugere que mitoK ATP não está diretamente relacionado à prevenção de TPM em cérebro, mas pode melhorar os níveis energéticos do tecido ao prevenir a hidrólise de ATP tecidual (Kowaltowski et al, 2006). …”

Section: +unclassified

See 4 more Smart Citations

Propriedades redox de canais de potássio mitocondriais ATP-sensíveis em cérebro de seu efeito neuroprotetor em excitotoxicidade

Fornazari¹

Self Cite

View full text Add to dashboard Cite

Section: Fluxo De K + E Canais De K + Mitocondriais Sensíveis a Atpunclassified

Section: Não Foi Observada Nenhuma Redução Nos Danos Causados Por Mmaunclassified

Section: Estudo Da Permeabilização Mitocondrial Induzida Por Ca 2+ Emunclassified

Section: +unclassified

See 3 more Smart Citations

Propriedades redox de canais de potássio mitocondriais ATP-sensíveis em cérebro de seu efeito neuroprotetor em excitotoxicidade

Fornazari¹

Self Cite

View full text Add to dashboard Cite

Mitochondrial potassium channels

Szewczyk

Jarmuszkiewicz

Kunz³

2009

IUBMB Life

163

114

View full text Add to dashboard Cite

SummaryMitochondrial potassium channels are believed to contribute to cytoprotection of injured cardiac and neuronal tissues. The following potassium channels have been described in the inner mitochondrial membrane: the ATP-regulated potassium channel, the large conductance Ca 21 -activated potassium channel, the voltage-gated Kv1.3 potassium channel, and the twin-pore domain TASK-3 potassium channel. The putative functional roles of these channels include changes in mitochondrial matrix volume, mitochondrial respiration, and membrane potential. In addition, the activity of these channels modulates the generation of reactive oxygen species by mitochondria. In this article, we discuss recent observations on three fundamental issues concerning mitochondrial potassium channels: (i) their molecular identity, (ii) their interaction with potassium channel openers and inhibitors, and (iii) their functional properties.

show abstract

Diazoxide ameliorates severity of experimental osteoarthritis by activating autophagy via modulation of the osteoarthritis‐related biomarkers

Meng

Shen

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Accumulating evidence suggests that autophagy plays a protective role in chondrocytes and prevents cartilage degeneration in osteoarthritis (OA). The objective of this study was to investigate the effect of diazoxide on chondrocyte death and cartilage degeneration and to determine whether these effects are correlated to autophagy in experimental OA. In this study, a cellular OA model was established by stimulating SW1353 cells with interleukin 1β. A rat OA model was generated by transecting the anterior cruciate ligament combined with the resection of the medial menisci, followed by treatment with diazoxide or diazoxide combination with 3-methyladenine. The percentage of viable cells was evaluated using calcein-acetoxymethyl/propidium iodide double staining. The messenger RNA expression levels of collagen type II alpha 1 chain (COL2A1), matrix metalloproteinase 13 (MMP-13), TIMP metallopeptidase inhibitor 1 (TIMP-1), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) were determined using quantitative real-time polymerase chain reaction. The cartilage thickness and joint space were evaluated using ultrasound. SW1353 cell degeneration and autophagosomes were observed using transmission electron microscopy. The expression levels of microtubule-associated protein 1 light chain 3 (LC3), beclin-1, P62, COL2A1, and MMP-13 were evaluated using immunofluorescence staining and Western blot analysis. Diazoxide significantly attenuated articular cartilage degeneration and SW1353 cell death in experimental OA. The restoration of autophagy was observed in the diazoxide-treated group. The beneficial effects of diazoxide were markedly blocked by 3-methyladenine. Diazoxide treatment also modulated the expression levels of OA-related biomarkers. These results demonstrated that diazoxide exerted a chondroprotective effect and attenuated cartilage degeneration by restoring autophagy via modulation of OA-related biomarkers in experimental OA. Diazoxide treatment might be a promising therapeutic approach to prevent the development of OA.

show abstract

Diazoxide protects against methylmalonate-induced neuronal toxicity

Cited by 26 publications

References 47 publications

Propriedades redox de canais de potássio mitocondriais ATP-sensíveis em cérebro de seu efeito neuroprotetor em excitotoxicidade

Propriedades redox de canais de potássio mitocondriais ATP-sensíveis em cérebro de seu efeito neuroprotetor em excitotoxicidade

Mitochondrial potassium channels

Diazoxide ameliorates severity of experimental osteoarthritis by activating autophagy via modulation of the osteoarthritis‐related biomarkers

Contact Info

Product

Resources

About