PMID- 12624307
OWN - NLM
STAT- MEDLINE
DCOM- 20030331
LR  - 20161122
IS  - 1524-4628 (Electronic)
IS  - 0039-2499 (Linking)
VI  - 34
IP  - 3
DP  - 2003 Mar
TI  - Selective neuromicrovascular endothelial cell death by 8-Iso-prostaglandin 
      F2alpha: possible role in ischemic brain injury.
PG  - 776-82
AB  - BACKGROUND AND PURPOSE: Free radical-induced peroxidation is an important factor 
      in the genesis of hypoxic-ischemic encephalopathy, including that of the preterm 
      infant. Isoprostanes are major peroxidation products. Since microvascular 
      dysfunction seems to contribute to ischemic encephalopathies, we studied the 
      cytotoxicity of 8-iso-prostaglandin F2alpha (PGF2alpha) on cerebral microvascular 
      cells. METHODS: Microvascular endothelial, astroglial, and smooth muscle cells 
      from newborn brain were cultured. The cytotoxicity of 8-iso-PGF2alpha on these 
      cells was determined by MTT assays and lactate dehydrogenase (LDH) release, 
      propidium iodide incorporation, and DNA fragmentation (terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling [TUNEL]). In addition, effects of 
      intraventricular injections of 8-iso-PGF2alpha and possible involvement of 
      thromboxane in 8-iso-PGF2alpha-induced cytotoxicity were determined. RESULTS: 
      8-Iso-PGF2alpha induced time- and concentration-dependent endothelial cell death 
      (EC50=0.1 nmol/L) but exerted little effect on smooth muscle and astroglial 
      cells; endothelial cell death seemed mostly of oncotic nature (propidium iodide 
      incorporation and LDH release). Cell death was associated with increased 
      endothelial thromboxane A2 (TXA2) formation and was prevented by TXA2 synthase 
      inhibitors (CGS12970 and U63557A); TXA2 mimetics U46619 and I-BOP also caused 
      endothelial cell death. Intraventricular injection of 8-iso-PGF2alpha induced 
      periventricular damage, which was attenuated by CGS12970 pretreatment. 
      CONCLUSIONS: These data disclose a novel action of 8-iso-PGF2alpha involving TXA2 
      in oxidant stress-induced cerebral microvascular injury and brain damage.
FAU - Brault, Sonia
AU  - Brault S
AD  - Centre de Recherche de l'Hopital Sainte-Justine, Department of Pediatrics and 
      Pharmacology, Universite de Montreal, Montreal, Quebec, Canada.
FAU - Martinez-Bermudez, Ana Katherine
AU  - Martinez-Bermudez AK
FAU - Marrache, Anne Marilise
AU  - Marrache AM
FAU - Gobeil, Fernand Jr
AU  - Gobeil F Jr
FAU - Hou, Xin
AU  - Hou X
FAU - Beauchamp, Martin
AU  - Beauchamp M
FAU - Quiniou, Christiane
AU  - Quiniou C
FAU - Almazan, Guillermina
AU  - Almazan G
FAU - Lachance, Christian
AU  - Lachance C
FAU - Roberts, Jackson 2nd
AU  - Roberts J 2nd
FAU - Varma, Daya R
AU  - Varma DR
FAU - Chemtob, Sylvain
AU  - Chemtob S
LA  - eng
GR  - GM42056/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030220
PL  - United States
TA  - Stroke
JT  - Stroke
JID - 0235266
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (F2-Isoprostanes)
RN  - 0 (Isoprostanes)
RN  - 27415-26-5 (8-epi-prostaglandin F2alpha)
RN  - 57576-52-0 (Thromboxane A2)
RN  - B7IN85G1HY (Dinoprost)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 5.3.99.5 (Thromboxane-A Synthase)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - W1ANC8Q5NW (8-isoprostaglandin E2)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/drug effects/metabolism
MH  - Brain/*blood supply/drug effects/pathology
MH  - Brain Ischemia/*metabolism
MH  - Cell Death/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - DNA Fragmentation/drug effects
MH  - *Dinoprost/*analogs & derivatives
MH  - Dinoprostone/*analogs & derivatives/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/cytology/*drug effects/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - F2-Isoprostanes/*pharmacology
MH  - In Vitro Techniques
MH  - Injections, Intraventricular
MH  - Isoprostanes/pharmacology
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Microcirculation/cytology/*drug effects/metabolism
MH  - Muscle, Smooth, Vascular/cytology/drug effects/metabolism
MH  - Necrosis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Swine
MH  - Thromboxane A2/metabolism
MH  - Thromboxane-A Synthase/antagonists & inhibitors
EDAT- 2003/03/08 04:00
MHDA- 2003/04/01 05:00
CRDT- 2003/03/08 04:00
PHST- 2003/03/08 04:00 [pubmed]
PHST- 2003/04/01 05:00 [medline]
PHST- 2003/03/08 04:00 [entrez]
AID - 01.STR.0000055763.76479.E6 [pii]
AID - 10.1161/01.STR.0000055763.76479.E6 [doi]
PST - ppublish
SO  - Stroke. 2003 Mar;34(3):776-82. doi: 10.1161/01.STR.0000055763.76479.E6. Epub 2003 
      Feb 20.