PMID- 18771709
OWN - NLM
STAT- MEDLINE
DCOM- 20081203
LR  - 20191210
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 444
IP  - 3
DP  - 2008 Oct 31
TI  - Baicalein suppresses hypoxia-induced HIF-1alpha protein accumulation and 
      activation through inhibition of reactive oxygen species and PI 3-kinase/Akt 
      pathway in BV2 murine microglial cells.
PG  - 264-9
LID - 10.1016/j.neulet.2008.08.057 [doi]
AB  - Hypoxia induces an inflammatory activation of microglia during cerebral ischemia. 
      The transcription factor of hypoxia-inducible genes hypoxia-inducible factor-1 
      (HIF-1) is known to be involved in inflammation and immune response. Although 
      baicalein (BE), a flavonoid, is shown to have anti-inflammatory effects and 
      attenuate ischemic injury, its action mechanism is not understood well. Thus, we 
      examined effect of BE on hypoxia-induced HIF-1 activation and its signaling 
      mechanism in BV2 microglial cells. BE inhibited hypoxia-induced HIF-1alpha 
      protein accumulation and HIF-1 transcriptional activation. Consistently, BE 
      suppressed hypoxia-induced expression of hypoxia responsive genes, iNOS, COX-2, 
      and VEGF. We then showed that BE inhibited hypoxia-induced phosphorylation of Akt 
      but not that of ERK and p38. Moreover, BE inhibited hypoxia-induced PI 3-kinase 
      activation. Finally, we showed that BE inhibited hypoxia-induced ROS generation, 
      and an antioxidant N-acetylcysteine reduced hypoxia-induced HIF-1alpha and iNOS 
      protein expression and PI 3-kinase/Akt activation in BV2 microglia. Taken 
      together, these results suggest that BE suppresses hypoxia-induced HIF-1alpha 
      protein and activation as well as expression of hypoxia responsive genes by 
      inhibiting ROS and PI 3-kinase/Akt pathway in BV2 microglia.
FAU - Hwang, Keun Young
AU  - Hwang KY
AD  - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee 
      University, Seoul 130-701, Republic of Korea.
FAU - Oh, Young Taek
AU  - Oh YT
FAU - Yoon, Hana
AU  - Yoon H
FAU - Lee, Jinhwa
AU  - Lee J
FAU - Kim, Hocheol
AU  - Kim H
FAU - Choe, Wonchae
AU  - Choe W
FAU - Kang, Insug
AU  - Kang I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080827
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Flavanones)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 49QAH60606 (baicalein)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Flavanones/*pharmacology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Mice
MH  - Microglia/*drug effects/metabolism
MH  - Nitric Oxide Synthase Type II/biosynthesis
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors
MH  - Rats
MH  - Reactive Oxygen Species/*antagonists & inhibitors
MH  - Transcriptional Activation
EDAT- 2008/09/06 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/09/06 09:00
PHST- 2008/07/03 00:00 [received]
PHST- 2008/08/19 00:00 [revised]
PHST- 2008/08/21 00:00 [accepted]
PHST- 2008/09/06 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/09/06 09:00 [entrez]
AID - S0304-3940(08)01176-2 [pii]
AID - 10.1016/j.neulet.2008.08.057 [doi]
PST - ppublish
SO  - Neurosci Lett. 2008 Oct 31;444(3):264-9. doi: 10.1016/j.neulet.2008.08.057. Epub 
      2008 Aug 27.