Propofol Decreases Endoplasmic Reticulum Stress-Mediated Apoptosis in Retinal Pigment Epithelial Cells.
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-eIF2α, and ATF4. Furthermore, it downregulated the expression of nuclear factor κB (NF-κB). 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.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Xuezhi
X
Zhou
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Yantao
Y
Wei
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Suo
S
Qiu
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Yue
Y
Xu
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Ting
T
Zhang
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Shaochong
S
Zhang
D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D019284:Thapsigargin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
C497109:ATF4 protein, human; D018686:Anesthetics, Intravenous; D000975:Antioxidants; C494826:BAX protein, human; C000595707:BCL2 protein, human; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D019284:Thapsigargin; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase; C506444:CASP12 protein, human; C505407:CASP3 protein, human; D053454:Caspase 12; D053148:Caspase 3; D002118:Calcium; D015742:Propofol