PMID- 21978097
OWN - NLM
STAT- MEDLINE
DCOM- 20120228
LR  - 20220310
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Linking)
VI  - 36
IP  - 12
DP  - 2011 Dec
TI  - Increased expression of tight junctions in ARPE-19 cells under endoplasmic 
      reticulum stress.
PG  - 1153-63
LID - 10.3109/02713683.2011.606592 [doi]
AB  - PURPOSE: To investigate the effects of endoplasmic reticulum (ER) stress on the 
      tight junctions of the retinal pigment epithelial (RPE) cells in vitro. MATERIALS 
      AND METHODS: ER stress was induced in cultured ARPE-19 cells, a human RPE cell 
      line, by exposure to tunicamycin (TM) or to thapsigargin (TG). After 6, 12, 24 
      and 48 hours of exposure, the expressions of GRP78/Bip (Bip), C/EBP-homologous 
      protein (CHOP), vascular endothelial growth factor (VEGF), zonula occludens 
      (ZO)-1, occludin and claudin-1 were determined by real-time RT-PCR. Immunoblot 
      analysis and/or immunohistochemistry for proteins of tight junctions and ER 
      stress markers, viz., Bip, activating transcription factor (ATF) 6, CHOP, and 
      caspase-4, were performed at 48 hours after the exposure. Enzyme-linked 
      immunosorbent assay was used to determine the concentration of VEGF165. 
      Transepithelial electrical resistance (TER) of the ARPE-19 cells was determined 
      to measure the permeability. RESULTS: The expressions of the mRNAs and/or 
      proteins of Bip, CHOP, ATF6 and caspase-4 were significantly increased in ARPE-19 
      cells under ER stress induced by TM and TG. The mRNAs of VEGF were also increased 
      by both TM and TG. However, the concentration of VEGF165 was not significantly 
      increased after 48 hours exposure to TM and TG compared to that of the control in 
      the apical chamber medium. The proteins and mRNAs of occludin and claudin-1 were 
      significantly increased by TM and TG, and that of ZO-1 was significantly 
      increased by TG. Immunohistochemistry showed that the staining of ZO-1, occludin 
      and claudin-1 under ER stress was stronger than that of the control. A 
      significant increase of TER was observed after exposure to TM and TG. 
      CONCLUSIONS: The increased expressions of tight junction molecules by TM- or 
      TG-exposed ARPE-19 cells indicate that ER stress can alter the function of RPE 
      cells and may be involved in the pathogenesis of age-related macular 
      degeneration.
FAU - Yoshikawa, Tadanobu
AU  - Yoshikawa T
AD  - Department of Ophthalmology, Kansai Medical University, Takii Hospital, Osaka, 
      Japan.
FAU - Ogata, Nahoko
AU  - Ogata N
FAU - Izuta, Hiroshi
AU  - Izuta H
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
FAU - Hara, Hideaki
AU  - Hara H
FAU - Takahashi, Kanji
AU  - Takahashi K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20111006
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Immunohistochemistry
MH  - Macular Degeneration/genetics/*metabolism/pathology
MH  - RNA, Messenger/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Retinal Pigment Epithelium/*metabolism/pathology
MH  - Tight Junctions/*genetics/metabolism
EDAT- 2011/10/08 06:00
MHDA- 2012/03/01 06:00
CRDT- 2011/10/08 06:00
PHST- 2011/10/08 06:00 [entrez]
PHST- 2011/10/08 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
AID - 10.3109/02713683.2011.606592 [doi]
PST - ppublish
SO  - Curr Eye Res. 2011 Dec;36(12):1153-63. doi: 10.3109/02713683.2011.606592. Epub 
      2011 Oct 6.