PMID- 31801685
OWN - NLM
STAT- MEDLINE
DCOM- 20200717
LR  - 20200717
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 190
DP  - 2020 Jan
TI  - Minocycline induces apoptosis of photoreceptor cells by regulating ER stress.
PG  - 107887
LID - S0014-4835(19)30479-8 [pii]
LID - 10.1016/j.exer.2019.107887 [doi]
AB  - Our previous work reported that minocycline induced inhibition of microglial 
      activation aggravated visual injury in an oxygen induced retinopathy animal 
      model. We hypothesized that minocycline might have aggravated injury to the 
      photoreceptor. Some patients who use minocycline to treat acne complain of visual 
      impairment; however, no studies have addressed minocycline toxicity to 
      photoreceptors. Here, we identified mechanistic effect of minocycline on 
      photoreceptor apoptosis. The results of Cell Counting Kit-8 and Ki67 staining 
      demonstrated that minocycline inhibited the proliferation of 661W cells, and flow 
      cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling 
      (TUNEL) demonstrated that minocycline promoted cell apoptosis. Additionally, 
      minocycline administration activated signaling associated with endoplasmic 
      reticulum stress, the pancreatic ER kinase-like ER kinase (PERK)-eukaryotic 
      translation initiation factor 2alpha (eIF2alpha)-CCAAT/enhancer-binding protein 
      homologous protein (CHOP) cascade, which represented the key mechanism underlying 
      the initiation of apoptosis. Moreover, we observed downregulated nuclear factor 
      erythroid 2-related factor 2 (Nrf2) after administration of minocycline for 12 h 
      (12 hours) and Nrf2 transferred from nuclear to cytoplasm after 6 h, indicating 
      that Nrf2 in nuclear may alleviated the pro-apoptotic effect of minocycline on 
      photoreceptor cells. Upregulating Nrf2 inhibited apoptosis in minocycline treated 
      661W cells. These represent the first data demonstrating minocycline toxicity to 
      photoreceptors via its pro-apoptotic effects through the regulation of ER stress 
      pathways.
CI  - Copyright (c) 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Xu, Wenqin
AU  - Xu W
AD  - Department of Ophthalmology, Eye Institute of China PLA, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, Shaanxi, PR China; The Orbital Disease 
      Institute of the Third Medical Center of PLA General Hospital, PR China. 
      Electronic address: 864644265@qq.com.
FAU - Tao, Mengzhang
AU  - Tao M
AD  - Department of Ophthalmology, Eye Institute of China PLA, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, Shaanxi, PR China.
FAU - Hu, Zhicha
AU  - Hu Z
AD  - The Orbital Disease Institute of the Third Medical Center of PLA General 
      Hospital, PR China.
FAU - Chang, Tianfang
AU  - Chang T
AD  - Department of Ophthalmology, Eye Institute of China PLA, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, Shaanxi, PR China.
FAU - Wang, Yusheng
AU  - Wang Y
AD  - Department of Ophthalmology, Eye Institute of China PLA, Xijing Hospital, Fourth 
      Military Medical University, Xi'an, Shaanxi, PR China. Electronic address: 
      wangys@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191201
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*toxicity
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Electroretinography
MH  - Endoplasmic Reticulum Stress/*drug effects/physiology
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - In Situ Nick-End Labeling
MH  - Intravitreal Injections
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Minocycline/*toxicity
MH  - NF-E2-Related Factor 2/metabolism
MH  - Photoreceptor Cells, Vertebrate/*drug effects/metabolism/pathology
MH  - Real-Time Polymerase Chain Reaction
MH  - eIF-2 Kinase/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Endoplasmic reticulum stress
OT  - Minocycline
OT  - Nrf2
OT  - Photoreceptor cells
EDAT- 2019/12/06 06:00
MHDA- 2020/07/18 06:00
CRDT- 2019/12/06 06:00
PHST- 2019/07/08 00:00 [received]
PHST- 2019/10/31 00:00 [revised]
PHST- 2019/11/25 00:00 [accepted]
PHST- 2019/12/06 06:00 [pubmed]
PHST- 2020/07/18 06:00 [medline]
PHST- 2019/12/06 06:00 [entrez]
AID - S0014-4835(19)30479-8 [pii]
AID - 10.1016/j.exer.2019.107887 [doi]
PST - ppublish
SO  - Exp Eye Res. 2020 Jan;190:107887. doi: 10.1016/j.exer.2019.107887. Epub 2019 Dec 
      1.