PMID- 18590709
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20211020
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1227
DP  - 2008 Aug 28
TI  - Neuroprotective effect of humanin on cerebral ischemia/reperfusion injury is 
      mediated by a PI3K/Akt pathway.
PG  - 12-8
LID - 10.1016/j.brainres.2008.06.018 [doi]
AB  - Humanin (HN) is an anti-apoptotic peptide that suppresses neuronal cell death 
      induced by Alzheimer's disease, prion protein fragments, and serum deprivation. 
      Recently, we demonstrated that Gly14-HN (HNG), a variant of HN in which the 14th 
      amino acid serine is replaced with glycine, can decrease apoptotic neuronal death 
      and reduce infarct volume in a focal cerebral ischemia/reperfusion mouse model. 
      In this study, we postulate that the mechanism of HNG's neuroprotective effect is 
      mediated by the PI3K/Akt pathway. Oxygen-glucose deprivation (OGD) was performed 
      in cultured mouse primary cortical neurons for 60 min. The effect of HNG and 
      PI3K/Akt inhibitors on OGD-induced cell death was examined at 24 h after 
      reperfusion. HNG increased cell viability after OGD in primary cortical neurons, 
      whereas the PI3K/Akt inhibitors wortmannin and Akti-1/2 attenuated the protective 
      effect of HNG. HNG rapidly increased Akt phosphorylation, an effect that was 
      inhibited by wortmannin and Akti-1/2. Mouse brains were injected 
      intraventricularly with HNG before being subjected to middle cerebral artery 
      occlusion (MCAO). HNG treatment significantly elevated p-Akt levels after 
      cerebral I/R injury and decreased infarct volume. The protective effect of HNG on 
      infarct size was attenuated by wortmannin and Akti-1/2. Taken as a whole, these 
      results suggest that PI3K/Akt activation mediates HNG's protective effect against 
      hypoxia/ischemia reperfusion injury.
FAU - Xu, Xingshun
AU  - Xu X
AD  - Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee 
      State University, Johnson City, TN 37614, USA.
FAU - Chua, Chu Chang
AU  - Chua CC
FAU - Gao, Jinping
AU  - Gao J
FAU - Chua, Kao-Wei
AU  - Chua KW
FAU - Wang, Hong
AU  - Wang H
FAU - Hamdy, Ronald C
AU  - Hamdy RC
FAU - Chua, Balvin H L
AU  - Chua BH
LA  - eng
GR  - R15 HL087271/HL/NHLBI NIH HHS/United States
GR  - R15 HL087271-01/HL/NHLBI NIH HHS/United States
GR  - HL087271/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080616
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Akt-I-1,2 compound)
RN  - 0 (Androstadienes)
RN  - 0 (Benzylamines)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinoxalines)
RN  - 0 (humanin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Benzylamines/pharmacology
MH  - Blotting, Western
MH  - Brain/drug effects/metabolism/pathology
MH  - Brain Ischemia/*complications
MH  - Cell Death/drug effects
MH  - Cell Hypoxia/physiology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Infarction/etiology/physiopathology/prevention & control
MH  - Glucose/metabolism/pharmacology
MH  - Infarction, Middle Cerebral Artery/complications/metabolism/pathology
MH  - Injections, Intraventricular
MH  - Intracellular Signaling Peptides and Proteins/administration & 
      dosage/*therapeutic use
MH  - Male
MH  - Mice
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/administration & dosage/*therapeutic use
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Quinoxalines/pharmacology
MH  - Reperfusion Injury/etiology/physiopathology/*prevention & control
MH  - Signal Transduction/drug effects
MH  - Wortmannin
PMC - PMC2575816
MID - NIHMS69517
EDAT- 2008/07/02 09:00
MHDA- 2008/12/17 09:00
PMCR- 2009/08/28
CRDT- 2008/07/02 09:00
PHST- 2008/04/28 00:00 [received]
PHST- 2008/06/08 00:00 [revised]
PHST- 2008/06/10 00:00 [accepted]
PHST- 2008/07/02 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/07/02 09:00 [entrez]
PHST- 2009/08/28 00:00 [pmc-release]
AID - S0006-8993(08)01444-3 [pii]
AID - 10.1016/j.brainres.2008.06.018 [doi]
PST - ppublish
SO  - Brain Res. 2008 Aug 28;1227:12-8. doi: 10.1016/j.brainres.2008.06.018. Epub 2008 
      Jun 16.