PMID- 20959717
OWN - NLM
STAT- MEDLINE
DCOM- 20110323
LR  - 20220408
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 42
IP  - 12
DP  - 2010 Dec 31
TI  - Baicalein protects HT22 murine hippocampal neuronal cells against endoplasmic 
      reticulum stress-induced apoptosis through inhibition of reactive oxygen species 
      production and CHOP induction.
PG  - 811-22
AB  - Baicalein is one of the major flavonoids in Scutellaria baicalensis Georgi and 
      possesses various effects, including cytoprotection and anti-inflammation. 
      Because endoplasmic reticulum (ER) stress has been implicated in 
      neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and 
      cerebral ischemia, we investigated the effects of baicalein on apoptotic death of 
      HT22 mouse hippocampal neuronal cells induced by thapsigargin (TG) and brefeldin 
      A (BFA), two representative ER stress inducers. Apoptosis, reactive oxygen 
      species (ROS) production, and mitochondrial membrane potential (MMP) were 
      measured by flow cytometry. Expression level and phosphorylation status of ER 
      stress-associated proteins and activation and cleavage of apoptosis-associated 
      proteins were analyzed by Western blot. Baicalein reduced TG- and BFA-induced 
      apoptosis of HT22 cells and activation and cleavage of apoptosis-associated 
      proteins, such as caspase-12 and -3 and poly(ADP-ribose) polymerase. Baicalein 
      also reduced the TG- and BFA-induced expression of ER stress-associated proteins, 
      including C/EBP homologous protein (CHOP) and glucose-regulated protein 78, the 
      cleavage of X-box binding protein-1 and activating transcription factor 6alpha, and 
      the phosphorylation of eukaryotic initiation factor-2alpha and mitogen-activated 
      protein kinases, such as p38, JNK, and ERK. Knock-down of CHOP expression by 
      siRNA transfection and specific inhibitors of p38 (SB203580), JNK (SP600125), and 
      ERK (PD98059) as well as anti-oxidant (N-acetylcysteine) reduced TG- or 
      BFA-induced cell death. Baicalein also reduced TG- and BFA-induced ROS 
      accumulation and MMP reduction. Taken together, these results suggest that 
      baicalein could protect HT22 neuronal cells against ER stress-induced apoptosis 
      by reducing CHOP induction as well as ROS accumulation and mitochondrial damage.
FAU - Choi, Ji Hyun
AU  - Choi JH
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, 
      Korea.
FAU - Choi, A Young
AU  - Choi AY
FAU - Yoon, Hana
AU  - Yoon H
FAU - Choe, Wonchae
AU  - Choe W
FAU - Yoon, Kyung-Sik
AU  - Yoon KS
FAU - Ha, Joohun
AU  - Ha J
FAU - Yeo, Eui-Ju
AU  - Yeo EJ
FAU - Kang, Insug
AU  - Kang I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Elf2 protein, mouse)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Flavanones)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factors)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 20350-15-6 (Brefeldin A)
RN  - 49QAH60606 (baicalein)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
ECI - Exp Mol Med. 2021 Apr;53(4):709. PMID: 33864027
MH  - Animals
MH  - *Apoptosis
MH  - Brefeldin A/pharmacology
MH  - Cell Line
MH  - Cytoprotection
MH  - DNA-Binding Proteins/metabolism
MH  - Endoplasmic Reticulum/drug effects/*physiology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Flavanones/*pharmacology
MH  - Heat-Shock Proteins/biosynthesis
MH  - Hippocampus/cytology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neurons/*drug effects/physiology
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/drug effects
MH  - Thapsigargin/pharmacology
MH  - Transcription Factor CHOP/*biosynthesis
MH  - Transcription Factors/metabolism
MH  - Unfolded Protein Response/drug effects
PMC - PMC3015155
EDAT- 2010/10/21 06:00
MHDA- 2011/03/24 06:00
PMCR- 2010/12/31
CRDT- 2010/10/21 06:00
PHST- 2010/10/21 06:00 [entrez]
PHST- 2010/10/21 06:00 [pubmed]
PHST- 2011/03/24 06:00 [medline]
PHST- 2010/12/31 00:00 [pmc-release]
AID - 10.3858/emm.2010.42.084 [pii]
AID - 10.3858/emm.2010.42.12.084 [doi]
PST - ppublish
SO  - Exp Mol Med. 2010 Dec 31;42(12):811-22. doi: 10.3858/emm.2010.42.12.084.