PMID- 20493918
OWN - NLM
STAT- MEDLINE
DCOM- 20101101
LR  - 20211203
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 57
IP  - 2
DP  - 2010 Sep
TI  - Apigenin protects HT22 murine hippocampal neuronal cells against endoplasmic 
      reticulum stress-induced apoptosis.
PG  - 143-52
LID - 10.1016/j.neuint.2010.05.006 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier Ltd. All rights reserved.
FAU - Choi, A Young
AU  - Choi AY
AD  - 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.
FAU - Choi, Ji Hyun
AU  - Choi JH
FAU - Lee, Jung Yeon
AU  - Lee JY
FAU - Yoon, Kyung-Sik
AU  - Yoon KS
FAU - Choe, Wonchae
AU  - Choe W
FAU - Ha, Joohun
AU  - Ha J
FAU - Yeo, Eui-Ju
AU  - Yeo EJ
FAU - Kang, Insug
AU  - Kang I
LA  - eng
PT  - Journal Article
DEP - 20100521
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Hspa5 protein, mouse)
RN  - 20350-15-6 (Brefeldin A)
RN  - 67526-95-8 (Thapsigargin)
RN  - 7V515PI7F6 (Apigenin)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
EIN - Neurochem Int. 2019 Oct;129:104458. PMID: 31101377
MH  - Animals
MH  - Apigenin/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Brefeldin A/pharmacology
MH  - Caspases/metabolism
MH  - Cell Line
MH  - Endoplasmic Reticulum/*drug effects/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Flow Cytometry
MH  - Hippocampus/cytology/*drug effects/metabolism
MH  - Hydrolysis
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Thapsigargin/pharmacology
EDAT- 2010/05/25 06:00
MHDA- 2010/11/03 06:00
CRDT- 2010/05/25 06:00
PHST- 2010/01/26 00:00 [received]
PHST- 2010/04/24 00:00 [revised]
PHST- 2010/05/10 00:00 [accepted]
PHST- 2010/05/25 06:00 [entrez]
PHST- 2010/05/25 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
AID - S0197-0186(10)00167-1 [pii]
AID - 10.1016/j.neuint.2010.05.006 [doi]
PST - ppublish
SO  - Neurochem Int. 2010 Sep;57(2):143-52. doi: 10.1016/j.neuint.2010.05.006. Epub 
      2010 May 21.