PMID- 18507737
OWN - NLM
STAT- MEDLINE
DCOM- 20080912
LR  - 20240312
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 106
IP  - 4
DP  - 2008 Aug
TI  - Endoplasmic reticulum Ca2+ dysregulation and endoplasmic reticulum stress 
      following in vitro neuronal ischemia: role of Na+-K+-Cl- cotransporter.
PG  - 1563-76
LID - 10.1111/j.1471-4159.2008.05501.x [doi]
AB  - We investigated the role of Na(+)-K(+)-Cl(-) cotransporter (NKCC1) in conjunction 
      with Na(+)/Ca(2+) exchanger (NCX) in disruption of endoplasmic reticulum (ER) 
      Ca(2+) homeostasis and ER stress development in primary cortical neurons 
      following in vitro ischemia. Oxygen-glucose deprivation (OGD) and reoxygenation 
      (REOX) caused a rise in [Na(+)](cyt) which was accompanied by an elevation in 
      [Ca(2+)](cyt). Inhibition of NKCC1 with its potent inhibitor bumetanide abolished 
      the OGD/REOX-induced rise in [Na(+)](cyt) and [Ca(2+)](cyt). Moreover, OGD 
      significantly increased Ca(2+)(ER) accumulation. Following REOX, a biphasic 
      change in Ca(2+)(ER) occurred with an initial release of Ca(2+)(ER) which was 
      sensitive to inositol 1,4,5-trisphosphate receptor (IP(3)R) inhibition and a 
      subsequent refilling of Ca(2+)(ER) stores. Inhibition of NKCC1 activity with its 
      inhibitor or genetic ablation prevented the release of Ca(2+)(ER). A similar 
      result was obtained with inhibition of reversed mode operation of NCX (NCX(rev)). 
      OGD/REOX also triggered a transient increase of glucose regulated protein 78 
      (GRP78), phospho-form of the alpha subunit of eukaryotic initiation factor 2 
      (p-eIF2alpha), and cleaved caspase 12 proteins. Pre-treatment of neurons with 
      NKCC1 inhibitor bumetanide inhibited upregulation of GRP78 and attenuated the 
      level of cleaved caspase 12 and p-eIF2alpha. Inhibition of NKCC1 reduced 
      cytochrome C release and neuronal death. Taken together, these results suggest 
      that NKCC1 and NCX(rev) may be involved in ischemic cell damage in part via 
      disrupting ER Ca(2+) homeostasis and ER function.
FAU - Chen, Xinzhi
AU  - Chen X
AD  - Neuroscience Training Program, and Department of Neurological Surgery, University 
      of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
FAU - Kintner, Douglas B
AU  - Kintner DB
FAU - Luo, Jing
AU  - Luo J
FAU - Baba, Akemichi
AU  - Baba A
FAU - Matsuda, Toshio
AU  - Matsuda T
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  - N0540154/PHS 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
DEP - 20080628
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Slc12a2 protein, mouse)
RN  - 0 (Sodium-Potassium-Chloride Symporters)
RN  - 0 (Solute Carrier Family 12, Member 2)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/*metabolism/pathology
MH  - Calcium/*metabolism
MH  - Cell Hypoxia/physiology
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum/pathology/*physiology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Female
MH  - Glucose/deficiency/genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/metabolism/*pathology
MH  - Oxidative Stress/*physiology
MH  - Pregnancy
MH  - Sodium-Potassium-Chloride 
      Symporters/biosynthesis/deficiency/genetics/metabolism/*physiology
MH  - Solute Carrier Family 12, Member 2
PMC - PMC2834254
MID - NIHMS171711
EDAT- 2008/05/30 09:00
MHDA- 2008/09/16 09:00
PMCR- 2010/03/08
CRDT- 2008/05/30 09:00
PHST- 2008/05/30 09:00 [pubmed]
PHST- 2008/09/16 09:00 [medline]
PHST- 2008/05/30 09:00 [entrez]
PHST- 2010/03/08 00:00 [pmc-release]
AID - JNC5501 [pii]
AID - 10.1111/j.1471-4159.2008.05501.x [doi]
PST - ppublish
SO  - J Neurochem. 2008 Aug;106(4):1563-76. doi: 10.1111/j.1471-4159.2008.05501.x. Epub 
      2008 Jun 28.