PMID- 12966327
OWN - NLM
STAT- MEDLINE
DCOM- 20040331
LR  - 20131121
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 27
IP  - 8
DP  - 2003 Aug
TI  - Human neural stem cells are more sensitive than astrocytes to ethanol exposure.
PG  - 1310-7
AB  - BACKGROUND: Exposure to ethanol (EtOH) can be deleterious to the developing 
      central nervous system. The mechanisms by which EtOH exposure induces neural 
      pathology in utero remain unclear. However, EtOH-induced increases in protein 
      kinase C (PKC) have been associated with apoptosis in human primary cell 
      cultures. Although the toxic effects of EtOH on differentiated neural cells have 
      been studied in laboratory animal models, the susceptibility of the human neural 
      stem cells (NSCs) that predominate in the central nervous system during embryonic 
      development has not been addressed. METHODS: For this study, fetal human brain 
      cells, which satisfied the criteria for NSCs by being CD133-positive, 
      nestin-positive, and differentiated glial fibrillary acidic protein-positive 
      human astrocytes, were studied. The cytotoxic potential of EtOH in NSC and 
      astrocyte cultures was studied by using morphological and biochemical methods. In 
      addition, membrane and cytosolic fraction PKC activity for each cell type was 
      assessed. RESULTS: NSC showed a dose-dependent increase in EtOH-induced toxicity 
      as estimated by terminal transferase-mediated dUTP nick end labeling (TUNEL) 
      stain and viability assays. TUNEL staining indicating DNA degradation consistent 
      with programmed (apoptotic) cell death was detectable in 90% of NSC 16 hr after 2 
      hr exposure to 10 mM EtOH. NSC also showed a concentration-dependent increase in 
      membrane, but not cytosol, PKC activity over the same EtOH dose range. By 
      contrast, astrocytes showed no cytotoxic effects at any concentrations of EtOH 
      used (0-10 mM). PKC activity of both the membrane and cytosolic fragments from 
      astrocytes also was unaffected by this range of doses. CONCLUSIONS: This study 
      demonstrates the susceptibility of human NSCs, compared with astrocytes, to EtOH 
      and indicates that alterations in PKC signal transduction in NSC may play a role 
      in EtOH-induced neuropathological processes.
FAU - Hao, Hsiao-Nan
AU  - Hao HN
AD  - Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, 
      USA. hsiao-nan.hao@crcm.med.wayne.edu
FAU - Parker, Graham C
AU  - Parker GC
FAU - Zhao, Jane
AU  - Zhao J
FAU - Barami, Kaveh
AU  - Barami K
FAU - Lyman, William D
AU  - Lyman WD
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (RNA, Messenger)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Astrocytes/*drug effects/metabolism
MH  - Brain/cytology/*drug effects/metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Ethanol/*pharmacology
MH  - Fetus
MH  - Humans
MH  - RNA, Messenger/biosynthesis
MH  - Stem Cells/*drug effects/metabolism
EDAT- 2003/09/11 05:00
MHDA- 2004/04/01 05:00
CRDT- 2003/09/11 05:00
PHST- 2003/09/11 05:00 [pubmed]
PHST- 2004/04/01 05:00 [medline]
PHST- 2003/09/11 05:00 [entrez]
AID - 10.1097/01.ALC.0000080671.56559.EF [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2003 Aug;27(8):1310-7. doi: 
      10.1097/01.ALC.0000080671.56559.EF.