PMID- 27311010
OWN - NLM
STAT- MEDLINE
DCOM- 20170726
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 6
DP  - 2016
TI  - Propofol Decreases Endoplasmic Reticulum Stress-Mediated Apoptosis in Retinal 
      Pigment Epithelial Cells.
PG  - e0157590
LID - 10.1371/journal.pone.0157590 [doi]
LID - e0157590
AB  - Age-related macular degeneration (AMD) is the major cause of loss of sight 
      globally. There is currently no effective treatment available. Retinal pigment 
      epithelial (RPE) cells are an important part of the outer blood-retina barrier 
      and their death is a determinant of AMD. Propofol, a common clinically used 
      intravenous anesthetic agent, has been shown to act as an efficacious 
      neuroprotective agent with antioxidative and anti-inflammatory properties in vivo 
      and in vitro. However, little is known about its effects on RPE cells. The 
      purpose of our research was to investigate whether propofol could protect RPE 
      cells from apoptosis through endoplasmic reticulum (ER) stress-dependent 
      pathways. To this end, prior to stimulation with thapsigargin (TG), ARPE-19 cells 
      were pretreated with varying concentrations of propofol. A protective effect of 
      propofol in TG-treated ARPE-9 was apparent, TUNEL and flow cytometric assays 
      showed decreased apoptosis. We further demonstrated that propofol pretreatment 
      attenuated or inhibited the effects caused by TG, such as upregulation of Bax, 
      BiP, C/EBP homologous protein (CHOP), active caspase 12, and cleaved caspase 3, 
      and downregulation of Bcl2. It also decreased the TG-induced levels of ER 
      stress-related molecules such as p-PERK, p-eIF2alpha, and ATF4. Furthermore, it 
      downregulated the expression of nuclear factor kappaB (NF-kappaB). This study elucidated 
      novel propofol-induced cellular mechanisms for antiapoptotic activities in RPE 
      cells undergoing ER stress and demonstrated the potential value of using propofol 
      in the treatment of AMD.
FAU - Zhou, Xuezhi
AU  - Zhou X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong, China.
FAU - Wei, Yantao
AU  - Wei Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong, China.
FAU - Qiu, Suo
AU  - Qiu S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong, China.
FAU - Xu, Yue
AU  - Xu Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong, China.
FAU - Zhang, Ting
AU  - Zhang T
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong, China.
FAU - Zhang, Shaochong
AU  - Zhang S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong, China.
LA  - eng
PT  - Journal Article
DEP - 20160616
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ATF4 protein, human)
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Antioxidants)
RN  - 0 (BAX protein, human)
RN  - 0 (BCL2 protein, human)
RN  - 0 (DDIT3 protein, human)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.1 (EIF2AK3 protein, human)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 3.4.22.- (CASP12 protein, human)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Caspase 12)
RN  - EC 3.4.22.- (Caspase 3)
RN  - SY7Q814VUP (Calcium)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Activating Transcription Factor 4/genetics/metabolism
MH  - Anesthetics, Intravenous/*pharmacology
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Calcium/metabolism
MH  - Caspase 12/genetics/metabolism
MH  - Caspase 3/genetics/metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/drug effects/genetics
MH  - Epithelial Cells/cytology/*drug effects/metabolism
MH  - Eukaryotic Initiation Factor-2/genetics/metabolism
MH  - Gene Expression Regulation
MH  - Heat-Shock Proteins/genetics/metabolism
MH  - Humans
MH  - NF-kappa B/genetics/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Propofol/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - Retinal Pigment Epithelium/cytology/drug effects/metabolism
MH  - Signal Transduction
MH  - Thapsigargin/antagonists & inhibitors/pharmacology
MH  - Transcription Factor CHOP/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
MH  - eIF-2 Kinase/genetics/metabolism
PMC - PMC4910991
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/06/17 06:00
MHDA- 2017/07/27 06:00
PMCR- 2016/06/16
CRDT- 2016/06/17 06:00
PHST- 2016/02/02 00:00 [received]
PHST- 2016/06/01 00:00 [accepted]
PHST- 2016/06/17 06:00 [entrez]
PHST- 2016/06/17 06:00 [pubmed]
PHST- 2017/07/27 06:00 [medline]
PHST- 2016/06/16 00:00 [pmc-release]
AID - PONE-D-15-53297 [pii]
AID - 10.1371/journal.pone.0157590 [doi]
PST - epublish
SO  - PLoS One. 2016 Jun 16;11(6):e0157590. doi: 10.1371/journal.pone.0157590. 
      eCollection 2016.