PMID- 9428515
OWN - NLM
STAT- MEDLINE
DCOM- 19980202
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 91
IP  - 7
DP  - 1997 Dec 26
TI  - Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of 
      laminin.
PG  - 917-25
AB  - Excess excitatory amino acids can provoke neuronal death in the hippocampus, and 
      the extracellular proteases tissue plasminogen activator (tPA) and plasmin (ogen) 
      have been implicated in this death. To investigate substrates for plasmin that 
      might influence neuronal degeneration, extracellular matrix (ECM) protein 
      expression was examined. Laminin is expressed in the hippocampus and disappears 
      after excitotoxin injection. Laminin disappearance precedes neuronal death, is 
      spatially coincident with regions that exhibit neuronal loss, and is blocked by 
      either tPA-deficiency or infusion of a plasmin inhibitor, both of which also 
      block neuronal degeneration. Preventing neuron-laminin interaction by infusion of 
      anti-laminin antibodies into tPA-deficient mice restores excitotoxic sensitivity 
      to their hippocampal neurons. These results indicate that disruption of 
      neuron-ECM interaction via tPA/plasmin catalyzed degradation of laminin 
      sensitizes hippocampal neurons to cell death.
FAU - Chen, Z L
AU  - Chen ZL
AD  - Department of Pharmacology, University at Stony Brook, New York 11794-8651, USA.
FAU - Strickland, S
AU  - Strickland S
LA  - eng
GR  - NS-35704/NS/NINDS 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.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Laminin)
RN  - 0 (Neurotoxins)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
RN  - EC 3.4.21.7 (Fibrinolysin)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Catalysis
MH  - *Cell Death/drug effects
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Fibrinolysin/*metabolism
MH  - Hippocampus/*cytology/drug effects
MH  - Kainic Acid/pharmacology
MH  - Laminin/*metabolism
MH  - Male
MH  - Mice
MH  - Neurons/*cytology/drug effects
MH  - Neurotoxins/pharmacology
MH  - Tissue Plasminogen Activator/deficiency
EDAT- 1998/01/15 00:00
MHDA- 1998/01/15 00:01
CRDT- 1998/01/15 00:00
PHST- 1998/01/15 00:00 [pubmed]
PHST- 1998/01/15 00:01 [medline]
PHST- 1998/01/15 00:00 [entrez]
AID - S0092-8674(00)80483-3 [pii]
AID - 10.1016/s0092-8674(00)80483-3 [doi]
PST - ppublish
SO  - Cell. 1997 Dec 26;91(7):917-25. doi: 10.1016/s0092-8674(00)80483-3.