Your browser doesn't support javascript.
loading
Dihydrolipoic Acid Inhibits Lysosomal Rupture and NLRP3 Through Lysosome-Associated Membrane Protein-1/Calcium/Calmodulin-Dependent Protein Kinase II/TAK1 Pathways After Subarachnoid Hemorrhage in Rat.
Zhou, Keren; Enkhjargal, Budbazar; Xie, Zhiyi; Sun, Chengmei; Wu, Lingyun; Malaguit, Jay; Chen, Sheng; Tang, Jiping; Zhang, Jianmin; Zhang, John H.
Afiliação
  • Zhou K; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Enkhjargal B; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Xie Z; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Sun C; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Wu L; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Malaguit J; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Chen S; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Tang J; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Zhang J; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
  • Zhang JH; From the Department of Neurosurgery, Second Affiliated Hospital, School of Medicine (K.Z., S.C., J.Z.), Brain research institute (K.Z., S.C., J.Z.), and Collaborative Innovation Center for Brain Science (K.Z., S.C., J.Z.), Zhejiang University, Hangzhou, China; and Department of Physiology and Pharma
Stroke ; 49(1): 175-183, 2018 01.
Article em En | MEDLINE | ID: mdl-29273596
ABSTRACT
BACKGROUND AND

PURPOSE:

The NLRP3 (nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome is a crucial component of the inflammatory response in early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated a role of dihydrolipoic acid (DHLA) in lysosomal rupture, NLRP3 activation, and determined the underlying pathway.

METHODS:

SAH was induced by endovascular perforation in male Sprague-Dawley rats. DHLA was administered intraperitoneally 1 hour after SAH. Small interfering RNA for lysosome-associated membrane protein-1 and CaMKIIα (calcium/calmodulin-dependent protein kinase II α) was administered through intracerebroventricular 48 hours before SAH induction. SAH grade evaluation, short- and long-term neurological function testing, Western blot, and immunofluorescence staining experiments were performed.

RESULTS:

DHLA treatment increased the expression of lysosome-associated membrane protein-1 and decreased phosphorylated CaMKIIα and NLRP3 inflammasome, thereby alleviating neurological deficits after SAH. Lysosome-associated membrane protein-1 small interfering RNA abolished the neuroprotective effects of DHLA and increased the level of phosphorylated CaMKIIα, p-TAK1 (phosphorylated transforming growth factor-ß-activated kinase), p-JNK (phosphorylated c-Jun-N-terminal kinase), and NLRP3 inflammasome. CaMKIIα small interfering RNA downregulated the expression of p-TAK1, p-JNK, and NLRP3 and improved the neurobehavior after SAH.

CONCLUSIONS:

DHLA treatment improved neurofunction and alleviated inflammation through the lysosome-associated membrane protein-1/CaMKII/TAK1 pathway in early brain injury after SAH. DHLA may provide a promising treatment to alleviate early brain injury after SAH.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hemorragia Subaracnóidea / Ácido Tióctico / MAP Quinase Quinase Quinases / Sistema de Sinalização das MAP Quinases / Proteínas de Membrana Lisossomal / Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina / Proteína 3 que Contém Domínio de Pirina da Família NLR / Lisossomos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hemorragia Subaracnóidea / Ácido Tióctico / MAP Quinase Quinase Quinases / Sistema de Sinalização das MAP Quinases / Proteínas de Membrana Lisossomal / Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina / Proteína 3 que Contém Domínio de Pirina da Família NLR / Lisossomos Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article