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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-7-12
pubmed:abstractText
Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson disease, and cerebral ischemia. In this study, we investigated the effects of apigenin on ER stress-induced apoptosis in murine HT22 hippocampal neuronal cells. Apigenin reduced apoptotic cell death of HT22 cells induced by thapsigargin (TG) and brefeldin A (BFA), two representative ER stress inducers. Consistent with these findings, apigenin blocked TG- and BFA-induced activation of caspase-12 and -3 and cleavage of poly (ADP-ribose) polymerase. Apigenin also reduced the TG- and BFA-induced expression of ER stress-associated proteins, including C/EBP homologous protein (CHOP), glucose-regulated protein (GRP) 78 and GRP94, the cleavage of activating transcription factor 6alpha, the phosphorylation of eukaryotic initiation factor 2alpha and inositol-requiring enzyme 1alpha, and the activation of mitogen-activated protein kinases, such as p38, c-Jun NH(2)-terminal kinase, and extracellular-regulated kinase. We also found that antioxidants such as N-acetylcysteine and glutathione blocked TG- and BFA-induced cell death and the expression of CHOP and GRP78. These results suggest that TG- and BFA-induced reactive oxygen species (ROS) accumulation plays an important role in ER stress-induced apoptosis. Apigenin also reduced TG- and BFA-induced ROS accumulation, suggesting that it exerts an antioxidant effect against ER stress inducers. Moreover, apigenin recovered TG- and BFA-induced reduction of the mitochondrial membrane potential in HT22 cells. Taken together, these results suggest that apigenin could protect HT22 neuronal cells against ER stress-induced apoptosis by reducing CHOP induction as well as ROS accumulation and mitochondrial damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1872-9754
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-52
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, School of Medicine, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, Biomedical Science Institute, Kyung Hee University, Seoul 130-701, Republic of Korea.
pubmed:publicationType
Journal Article