PMID- 21568938
OWN - NLM
STAT- MEDLINE
DCOM- 20120118
LR  - 20220615
IS  - 1573-4935 (Electronic)
IS  - 0144-8463 (Linking)
VI  - 31
IP  - 6
DP  - 2011 Dec
TI  - Permissive effect of EGFR-activated pathways on RVI and their anti-apoptotic 
      effect in hypertonicity-exposed mIMCD3 cells.
PG  - 489-97
LID - 10.1042/BSR20110024 [doi]
AB  - Hypertonicity is a stressful stimulus leading to cell shrinkage and apoptotic 
      cell death. Apoptosis can be prevented if cells are able to activate the 
      mechanism of RVI (regulatory volume increase). This study in mIMCD3 cells 
      presents evidence of a permissive role of the EGFR (epidermal growth factor 
      receptor) on RVI, achieved for the most part through the two main EGFR-triggered 
      signalling chains, the MAPK (mitogen-activated protein kinase)/ERK 
      (extracellular-signal-regulated kinase) and the PI3K (phosphoinositide 
      3-kinase)/Akt (also known as protein kinase B) pathways. Hyperosmotic solutions 
      (450 mosM) made by addition of NaCl, increased EGFR phosphorylation, which is 
      prevented by GM6001 and AG1478, blockers respectively, of MMPs (matrix 
      metalloproteinases) and EGFR. Inhibition of EGFR, ERK (PD98059) or PI3K/Akt 
      (wortmannin) phosphorylation reduced RVI by 60, 48 and 58% respectively. The NHE 
      (Na(+)/H(+) exchanger) seems to be the essential mediator of this effect since 
      (i) NHE is the main contributor to RVI, (ii) EGFR, ERK and PI3K/Akt blockers 
      added together with the NHE blocker zoniporide reduce RVI by non-additive effects 
      and (iii) All the blockers significantly lowered the NHE rate in cells challenged 
      by an NH(4)Cl pulse. Besides reducing RVI, the inhibition of MMP, EGFR and 
      PI3K/Akt had a strong pro-apoptotic effect increasing cell death by 2-3.7-fold. 
      This effect was significantly lower when RVI inhibition did not involve the 
      EGFR-PI3K/Akt pathway. These results provide evidence that Akt and its permissive 
      effect on RVI have a predominant influence on cell survival under hypertonic 
      conditions in IMCD3 cells. This role of Akt operates under the influence of EGFR 
      activation, promoted by MMP.
CI  - (c) The Authors Journal compilation (c) 2011 Biochemical Society
FAU - Ruiz-Martinez, Alejandro
AU  - Ruiz-Martinez A
AD  - Division de Neurociencias, Instituto de Fisiologia Celular, Universidad Nacional 
      Autonoma de Mexico, Mexico City, Mexico.
FAU - Vazquez-Juarez, Erika
AU  - Vazquez-Juarez E
FAU - Ramos-Mandujano, Gerardo
AU  - Ramos-Mandujano G
FAU - Pasantes-Morales, Herminia
AU  - Pasantes-Morales H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biosci Rep
JT  - Bioscience reports
JID - 8102797
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Saline Solution, Hypertonic)
RN  - 0 (Slc9c1 protein, mouse)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Cell Line
MH  - *Cell Size
MH  - Enzyme Activation
MH  - ErbB Receptors/antagonists & inhibitors/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/physiology
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism
MH  - Saline Solution, Hypertonic/*administration & dosage
MH  - Signal Transduction
MH  - Sodium-Hydrogen Exchangers/antagonists & inhibitors/*metabolism
EDAT- 2011/05/17 06:00
MHDA- 2012/01/19 06:00
CRDT- 2011/05/17 06:00
PHST- 2011/05/17 06:00 [entrez]
PHST- 2011/05/17 06:00 [pubmed]
PHST- 2012/01/19 06:00 [medline]
AID - BSR20110024 [pii]
AID - 10.1042/BSR20110024 [doi]
PST - ppublish
SO  - Biosci Rep. 2011 Dec;31(6):489-97. doi: 10.1042/BSR20110024.