PMID- 19840218
OWN - NLM
STAT- MEDLINE
DCOM- 20100208
LR  - 20211020
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 112
IP  - 1
DP  - 2010 Jan
TI  - Protein aggregation in neurons following OGD: a role for Na+ and Ca2+ ionic 
      dysregulation.
PG  - 173-82
LID - 10.1111/j.1471-4159.2009.06438.x [doi]
AB  - In this study, we investigated whether disruption of Na(+) and Ca(2+) homeostasis 
      via activation of Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and reversal 
      of Na(+)/Ca(2+) exchange (NCX(rev)) affects protein aggregation and degradation 
      following oxygen-glucose deprivation (OGD). Cultured cortical neurons were 
      subjected to 2 h OGD and 1-24 h reoxygenation (REOX). Redistribution of ubiquitin 
      and formation of ubiquitin-conjugated protein aggregates occurred in neurons as 
      early as 2 h REOX. The protein aggregation progressed further by 8 h REOX. There 
      was no significant recovery at 24 h REOX. Moreover, the proteasome activity in 
      neurons was inhibited by 80-90% during 2-8 h REOX and recovered partially at 24 h 
      REOX. Interestingly, pharmacological inhibition or genetic ablation of NKCC1 
      activity significantly decreased accumulation of ubiquitin-conjugated protein 
      aggregates and improved proteasome activity. A similar protective effect was 
      obtained by blocking NCX(rev) activity. Inhibition of NKCC1 activity also 
      preserved intracellular ATP and Na(+) homeostasis during 0-24 h REOX. In a 
      positive control study, disruption of endoplasmic reticulum Ca(2+) with 
      thapsigargin triggered redistribution of free ubiquitin and protein aggregation. 
      We conclude that overstimulation of NKCC1 and NCX(rev) following OGD/REOX 
      partially contributes to protein aggregation and proteasome dysfunction as a 
      result of ionic dysregulation.
FAU - Chen, Xinzhi
AU  - Chen X
AD  - Neuroscience Training Program, University of Wisconsin School of Medicine and 
      Public Health, Waisman Center, Madison, Wisconsin, USA.
FAU - Kintner, Douglas B
AU  - Kintner DB
FAU - Baba, Akemichi
AU  - Baba A
FAU - Matsuda, Toshio
AU  - Matsuda T
FAU - Shull, Gary E
AU  - Shull GE
FAU - Sun, Dandan
AU  - Sun D
LA  - eng
GR  - R01 NS038118-04A1/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-07/NS/NINDS NIH HHS/United States
GR  - R01 NS048216-03/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-06/NS/NINDS NIH HHS/United States
GR  - R01 NS038118/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-09/NS/NINDS NIH HHS/United States
GR  - R01 NS048216-04/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-02/NS/NINDS NIH HHS/United States
GR  - R01NS048216/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-08A2S1/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-03/NS/NINDS NIH HHS/United States
GR  - R01 NS048216-02/NS/NINDS NIH HHS/United States
GR  - R01NS38118/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-01A1/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-08A2/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-05/NS/NINDS NIH HHS/United States
GR  - R01 NS048216-01A1/NS/NINDS NIH HHS/United States
GR  - R01 NS038118-02S1/NS/NINDS NIH HHS/United States
GR  - R01 NS048216-05A1/NS/NINDS NIH HHS/United States
GR  - R01 NS048216/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091015
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Cations, Divalent)
RN  - 0 (Cations, Monovalent)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Slc12a2 protein, mouse)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*physiology
MH  - Cations, Divalent/antagonists & inhibitors/metabolism
MH  - Cations, Monovalent/antagonists & inhibitors/metabolism
MH  - Cell Hypoxia/physiology
MH  - Cells, Cultured
MH  - Female
MH  - Glucose/deficiency
MH  - Homeostasis/genetics/physiology
MH  - Hypoxia/metabolism
MH  - Membrane Transport Proteins/*metabolism/physiology
MH  - Mice
MH  - Neurons/*metabolism/physiology
MH  - Pregnancy
MH  - Proteasome Endopeptidase Complex/physiology
MH  - Proteasome Inhibitors
MH  - Protein Folding
MH  - Protein Multimerization
MH  - Sodium/*physiology
MH  - Sodium-Potassium-Chloride Symporters/deficiency/genetics/metabolism
MH  - Solute Carrier Family 12, Member 2
PMC - PMC2817933
MID - NIHMS171703
EDAT- 2009/10/21 06:00
MHDA- 2010/02/09 06:00
PMCR- 2011/01/01
CRDT- 2009/10/21 06:00
PHST- 2009/10/21 06:00 [entrez]
PHST- 2009/10/21 06:00 [pubmed]
PHST- 2010/02/09 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - JNC6438 [pii]
AID - 10.1111/j.1471-4159.2009.06438.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 Jan;112(1):173-82. doi: 10.1111/j.1471-4159.2009.06438.x. Epub 
      2009 Oct 15.