PMID- 18515580
OWN - NLM
STAT- MEDLINE
DCOM- 20080718
LR  - 20161124
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 49
IP  - 6
DP  - 2008 Jun
TI  - Induction of amyloid beta accumulation by ER calcium disruption and resultant 
      upregulation of angiogenic factors in ARPE19 cells.
PG  - 2376-83
LID - 10.1167/iovs.07-1067 [doi]
AB  - PURPOSE: To investigate the intracellular mechanisms that induce amyloid beta 
      (Abeta) accumulation and angiogenesis in the human retinal pigment epithelial 
      cell line ARPE19. METHODS: The authors used two endoplasmic reticulum (ER) 
      stress-inducing reagents, thapsigargin (TG), which inhibits the 
      sarcoplasmic/endoplasmic calcium (Ca)2+-ATPase, and tunicamycin (TM), which 
      inhibits N-linked glycosylation. The expression pattern of Abeta-precursor 
      protein (APP) splice variants was investigated by reverse transcription (RT)-PCR. 
      Cellular expressions of both a series of Abeta metabolism-related factors and 
      angiogenic factors were evaluated by real-time RT-PCR and Western blot (VEGF). 
      Expression of caspase-4 was examined by real-time RT-PCR and Western blot to 
      evaluate the effect of the ER stressor. Intracellular Ca elevation by TG was 
      evaluated by Ca2+ imaging experiments. Dimethyl sulfoxide and staurosporine were 
      used as a nonreagent control and as an apoptosis-inducing reagent through 
      mitochondria not ER, respectively. RESULTS: TG-treated ARPE19 cells increased the 
      mRNA expression of Abeta production-inducing APP splice variants and reduced that 
      of neprilysin, a catabolic enzyme for Abeta. TG-treated ARPE19 cells produced 
      increases in VEGF, TNF-alpha, TACE mRNA, and VEGF protein expressions and a 
      decrease in PEDF mRNA expression. TG-treated ARPE19 cells induced the expression 
      of active more than TM-treated casepase-4. The intracellular Ca concentration was 
      elevated in only TG-treated ARPE19 cells. CONCLUSIONS: TG-treated ARPE19 cells 
      showed both Abeta accumulation-inducible and angiogenic factor mRNA expression 
      patterns. This study suggests the possibility that ER stress through ER calcium 
      disruption may induce the expression not only of Abeta deposit-promoting factors 
      but also angiogenic factors in the retinal pigment epithelium.
FAU - Koyama, Yoshihisa
AU  - Koyama Y
AD  - Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka 
      University, Suita, Osaka, Japan.
FAU - Matsuzaki, Shinsuke
AU  - Matsuzaki S
FAU - Gomi, Fumi
AU  - Gomi F
FAU - Yamada, Kohei
AU  - Yamada K
FAU - Katayama, Taiichi
AU  - Katayama T
FAU - Sato, Kohji
AU  - Sato K
FAU - Kumada, Tatsuro
AU  - Kumada T
FAU - Fukuda, Atsuo
AU  - Fukuda A
FAU - Matsuda, Satoshi
AU  - Matsuda S
FAU - Tano, Yasuo
AU  - Tano Y
FAU - Tohyama, Masaya
AU  - Tohyama M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Angiogenic Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Eye Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serpins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (pigment epithelium-derived factor)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.22.- (CASP4 protein, human)
RN  - EC 3.4.22.- (Caspases, Initiator)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - ADAM Proteins/genetics
MH  - ADAM17 Protein
MH  - Amyloid beta-Peptides/*biosynthesis/genetics
MH  - Amyloid beta-Protein Precursor
MH  - Angiogenic Proteins/genetics/*metabolism
MH  - Blotting, Western
MH  - Calcium/*metabolism
MH  - Caspases, Initiator/genetics
MH  - Cell Line
MH  - Endoplasmic Reticulum/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Eye Proteins/genetics
MH  - Humans
MH  - Nerve Growth Factors/genetics
MH  - Pigment Epithelium of Eye/*drug effects/metabolism
MH  - Protein Isoforms/genetics
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Serpins/genetics
MH  - Thapsigargin/*pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Tunicamycin/*pharmacology
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/genetics
EDAT- 2008/06/03 09:00
MHDA- 2008/07/19 09:00
CRDT- 2008/06/03 09:00
PHST- 2008/06/03 09:00 [pubmed]
PHST- 2008/07/19 09:00 [medline]
PHST- 2008/06/03 09:00 [entrez]
AID - 49/6/2376 [pii]
AID - 10.1167/iovs.07-1067 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2376-83. doi: 10.1167/iovs.07-1067.