PMID- 12237337
OWN - NLM
STAT- MEDLINE
DCOM- 20021011
LR  - 20190607
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 62
IP  - 4
DP  - 2002 Oct
TI  - Regulation of the neuronal glutamate transporter excitatory amino acid carrier-1 
      (EAAC1) by different protein kinase C subtypes.
PG  - 901-10
AB  - In previous studies, we have shown that activation of protein kinase C (PKC) 
      rapidly (within minutes) increases the activity and cell surface expression of 
      the glutamate transporter EAAC1 in two systems that endogenously express this 
      transporter (C6 glioma cells and cocultures of neurons and astrocytes). However, 
      the magnitude of the increase in activity is greater than the increase in cell 
      surface expression. In addition, certain compounds completely block the increase 
      in cell surface expression but only partially attenuate the increase in activity. 
      We hypothesized that PKC increases EAAC1 activity by increasing cell surface 
      expression and catalytic efficiency and that two different subtypes of PKC 
      mediate these effects. To address these hypotheses, the PKC subtypes expressed by 
      C6 glioma cells were identified. Of the PKC subtypes that are activated by 
      phorbol esters, only PKCalpha, PKCdelta, and PKCepsilon were observed. Go6976, a 
      compound that blocks PKCalpha at concentrations that do not inhibit PKCdelta or 
      PKCepsilon, partially inhibited the increase in uptake but completely abolished 
      the increase in EAAC1 cell surface expression. The 'Go6976-insensitive' increase 
      in activity was not associated with a change in total transporter expression but 
      was associated with an increase in the V(max). Na(+)-dependent glycine transport 
      was not increased, providing indirect evidence that the Go6976-insensitive 
      increase in activity was not caused by a change in the Na(+) electrochemical 
      gradient required for activity. Finally, by down-regulating different subtypes of 
      PKC, we found evidence that PKCepsilon mediates the increase in EAAC1 activity 
      that is independent of changes in cell surface expression and found further 
      evidence that PKCalpha mediates the increase in cell surface expression. The 
      potential relationship of the present work with a previously identified role for 
      PKCalpha in certain forms of synaptic plasticity is discussed.
FAU - Gonzalez, Marco I
AU  - Gonzalez MI
AD  - Department of Pediatrics and Pharmacology, Children's Hospital of Philadelphia, 
      University of Pennsylvania, Philadelphia, Pennsylvania, USA.
FAU - Kazanietz, Marcelo G
AU  - Kazanietz MG
FAU - Robinson, Michael B
AU  - Robinson MB
LA  - eng
GR  - NS29868/NS/NINDS NIH HHS/United States
GR  - NS36465/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Bryostatins)
RN  - 0 (Carbazoles)
RN  - 0 (Carcinogens)
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Excitatory Amino Acid Transporter 3)
RN  - 0 (Glutamate Plasma Membrane Transport Proteins)
RN  - 0 (Indoles)
RN  - 0 (Lactones)
RN  - 0 (Macrolides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Slc1a1 protein, rat)
RN  - 0 (Symporters)
RN  - 136194-77-9 (Go 6976)
RN  - 37O2X55Y9E (bryostatin 1)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Transport System X-AG/*metabolism
MH  - Animals
MH  - Bryostatins
MH  - Carbazoles/pharmacology
MH  - Carcinogens/pharmacology
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Excitatory Amino Acid Transporter 3
MH  - Female
MH  - Glutamate Plasma Membrane Transport Proteins
MH  - Indoles/pharmacology
MH  - Lactones/pharmacology
MH  - Macrolides
MH  - Neurons/*metabolism
MH  - Protein Kinase C/antagonists & inhibitors/classification/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Cell Surface/biosynthesis
MH  - *Symporters
MH  - Tetradecanoylphorbol Acetate/pharmacology
EDAT- 2002/09/19 10:00
MHDA- 2002/10/12 04:00
CRDT- 2002/09/19 10:00
PHST- 2002/09/19 10:00 [pubmed]
PHST- 2002/10/12 04:00 [medline]
PHST- 2002/09/19 10:00 [entrez]
AID - 10.1124/mol.62.4.901 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2002 Oct;62(4):901-10. doi: 10.1124/mol.62.4.901.