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Neurotoxin ß­N­methylamino­L­alanine induces endoplasmic reticulum stress­mediated neuronal apoptosis.
Shen, Haiying; Kim, Kiyoon; Oh, Yoojung; Yoon, Kyung Sik; Baik, Hyung Hwan; Kim, Sung Soo; Ha, Joohun; Kang, Insug; Choe, Wonchae.
Afiliação
  • Shen H; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Kim K; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Oh Y; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Yoon KS; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Baik HH; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Kim SS; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Ha J; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Kang I; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
  • Choe W; Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130­701, Republic of Korea.
Mol Med Rep ; 14(5): 4873-4880, 2016 Nov.
Article em En | MEDLINE | ID: mdl-27748814
ABSTRACT
ß-N-methylamino-L-alanine (BMAA) is a neurotoxin that is closely associated with the incidence of amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. In cultured neuronal cells, BMAA notably induces the upregulation of endoplasmic reticulum (ER) chaperons and activates the unfolded protein response (UPR) receptor pathways of protein kinase RNA­like endoplasmic reticulum kinase, inositol­requiring kinase 1 and transcription factor 6. The ER stress­specific protein CCAAT/­enhancer­binding protein homologous protein (CHOP) affords pro­apoptotic responses that cause mitochondrial damage and caspase activation. BMAA also induces the activation of mitogen­activated protein kinase member c­JUN N­terminal kinase, p38 and extracellular signal­regulated kinase, which have been suggested to be involved in the signaling pathway of UPR­mediated apoptosis. Inhibition of ER stress using ER stress antagonist, salubrinal, attenuated the expression of CHOP and alleviated neuronal death. Overexpression of heat shock protein 70 suppressed the activation of UPR receptors and UPR­evoked apoptotic signaling. The present findings demonstrated that ER stress induced by BMAA is the important mediator of neuronal injury and apoptotic death, and suggests development in novel therapeutic strategies for treatment.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estresse do Retículo Endoplasmático / Diamino Aminoácidos / Neurônios / Neurotoxinas Limite: Animals / Humans Idioma: En Revista: Mol Med Rep Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estresse do Retículo Endoplasmático / Diamino Aminoácidos / Neurônios / Neurotoxinas Limite: Animals / Humans Idioma: En Revista: Mol Med Rep Ano de publicação: 2016 Tipo de documento: Article
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