PMID- 22705154
OWN - NLM
STAT- MEDLINE
DCOM- 20121119
LR  - 20171116
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1823
IP  - 10
DP  - 2012 Oct
TI  - ERK1/2-dependent bestrophin-3 expression prevents ER-stress-induced cell death in 
      renal epithelial cells by reducing CHOP.
PG  - 1864-76
LID - 10.1016/j.bbamcr.2012.06.003 [doi]
AB  - Upon endoplasmic reticulum (ER) stress induction, cells endeavor to survive by 
      engaging the adaptive stress response known as the unfolded protein response or 
      by removing aggregated proteins via autophagy. Chronic ER stress culminates in 
      apoptotic cell death, which involves induction of pro-apoptotic CHOP. Here, we 
      show that bestrophin-3 (Best-3), a protein previously associated with 
      Ca(2+)-activated Cl(-) channel activity, is upregulated by the ER stressors, 
      thapsigargin (TG), tunicamycin (TUN) and the toxic metal Cd(2+). In cultured rat 
      kidney proximal tubule cells, ER stress, CHOP and cell death were induced after 
      6h by Cd(2+) (25muM), TG (3muM) and TUN (6muM), were associated with increased 
      cytosolic Ca(2+) and downstream formation of reactive oxygen species and 
      attenuated by the Ca(2+) chelator BAPTA-AM (10muM), the antioxidant alpha-tocopherol 
      (100muM), or overexpression of catalase (CAT). Immunofluorescence staining showed 
      Best-3 expression in the plasma membrane, nuclei and intracellular compartments, 
      though not in the ER, in cultured cells and rat kidney cortex sections. Best-3 
      mRNA was augmented by ER stress and signaled through increased Ca(2+), oxidative 
      stress and ERK1/2 phosphorylation, because it was attenuated by alpha-tocopherol, CAT 
      expression, BAPTA-AM, calmodulin kinase inhibitor calmidazolium (40muM), ERK1/2 
      inhibitor U0126 (10muM), and ERK1/2 RNAi. Knockdown of Best-3 resulted in 
      decreased cell number consequentially of cell death, as determined by nuclear 
      staining and PARP-1 cleavage. Furthermore, reduced ER stress-cell death by Best-3 
      overexpression is attributed to diminished CHOP. Since Best-3 overexpression did 
      not affect upstream signaling pathways, we hypothesize that Best-3 possibly 
      interferes with CHOP transcription. From our novel observations, we conclude that 
      ERK1/2-dependent Best-3 activation regulates cell fate decisions during ER stress 
      by suppressing CHOP induction and death.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Lee, Wing-Kee
AU  - Lee WK
AD  - Institute of Physiology & Pathophysiology, ZBAF, University of Witten/Herdecke, 
      Witten, Germany. wing-kee.lee@uni-wh.de
FAU - Chakraborty, Prabir K
AU  - Chakraborty PK
FAU - Roussa, Eleni
AU  - Roussa E
FAU - Wolff, Natascha A
AU  - Wolff NA
FAU - Thevenod, Frank
AU  - Thevenod F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120613
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Best3 protein, rat)
RN  - 0 (Bestrophins)
RN  - 0 (Chloride Channels)
RN  - 0 (Reactive Oxygen Species)
RN  - 00BH33GNGH (Cadmium)
RN  - 11089-65-9 (Tunicamycin)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Bestrophins
MH  - Cadmium/toxicity
MH  - Calcium/metabolism
MH  - Cell Death/drug effects
MH  - Cell Lineage/drug effects
MH  - Cell Membrane/drug effects/metabolism
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chloride Channels/genetics/*metabolism
MH  - Cytoprotection/drug effects
MH  - *Endoplasmic Reticulum Stress/drug effects
MH  - Enzyme Activation/drug effects
MH  - Epithelial Cells/drug effects/*enzymology/*pathology
MH  - Kidney
MH  - Kinetics
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Models, Biological
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Thapsigargin/pharmacology
MH  - Transcription Factor CHOP/*metabolism
MH  - Tunicamycin/pharmacology
MH  - Unfolded Protein Response/drug effects
MH  - Up-Regulation/drug effects
EDAT- 2012/06/19 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/19 06:00
PHST- 2011/09/19 00:00 [received]
PHST- 2012/06/04 00:00 [revised]
PHST- 2012/06/05 00:00 [accepted]
PHST- 2012/06/19 06:00 [entrez]
PHST- 2012/06/19 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - S0167-4889(12)00158-9 [pii]
AID - 10.1016/j.bbamcr.2012.06.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2012 Oct;1823(10):1864-76. doi: 
      10.1016/j.bbamcr.2012.06.003. Epub 2012 Jun 13.