PMID- 36617838
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20230111
IS  - 1578-1267 (Electronic)
IS  - 0301-0546 (Linking)
VI  - 51
IP  - 1
DP  - 2023
TI  - NLRX1 increases human retinal pigment epithelial autophagy and reduces 
      H(2)O(2)-induced oxidative stress and inflammation by suppressing FUNDC1 
      phosphorylation and NLRP3 activation.
PG  - 177-186
LID - 10.15586/aei.v51i1.766 [doi]
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of impaired 
      vision as well as some earlier effects, such as reading and face recognition. 
      Oxidative damage and inflammation of retinal pigment epithelial (RPE) cells are 
      major causes of AMD. Additionally, autophagy in RPE cells can lead to cellular 
      homeostasis under oxidative stress. Nucleotide-binding oligomerization domain 
      (NOD)-like receptor X1 (NLRX1) is a mysterious modulator of the immune system 
      function which inhibits inflammatory response, attenuates reactive oxygen species 
      (ROS) production, and regulates autophagy. This study attempted to explore the 
      role of NLRX1 in oxidative stress, inflammation, and autophagy in AMD. METHODS: 
      An in vitro model of AMD was built in human retinal pigment epithelial cell line 
      19 (ARPE-19) treated with H(2)O(2). The cell viability, NLRX1 expressions, levels 
      of superoxide dismutase (SOD), glutathione (GHS), and ROS, concentrations of 
      interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, and monocyte 
      chemoattractant protein-1 (MCP-1), expressions of NLRX1, p62, LC3-II/LC3-I, 
      FUNDC1, and NOD-like receptor protein 3 (NLRP3) inflammasome were expounded by 
      cell counting kit-8, colorimetric, enzyme-linked immunosorbent serologic assay 
      (ELISA), and Western blot assay. RESULTS: H(2)O(2) treatment notably reduced the 
      relative protein expression of NLRX1. Meanwhile, H(2)O(2) incubation decreased 
      cell viability, diminished SOD and GSH concentrations, accompanied with the 
      increased level of ROS, enhanced IL-1beta, TNF-alpha, IL-6, and MCP-1 concentrations, 
      and aggrandized the relative protein expression of p62 with reduced LC3-II/LC3-I 
      ratio. Moreover, these results were further promoted with knockdown of NLRX1 and 
      reversed with overexpression. Mechanically, silencing of NLRX1 further observably 
      enhanced the relative levels of -phosphorylated FUNDC1/FUNDC1, and NLRP3 
      inflammasome-related proteins, while overexpression of NLRX1 exhibited inverse 
      results in the H(2)O(2)-induced ARPE-19 cells. CONCLUSION: NLRX1 suppressed 
      H(2)O(2)-induced oxidative stress and inflammation, and facilitated autophagy by 
      suppressing FUNDC1 phosphorylation and NLRP3 activation in ARPE-19 cells.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Ophthalmology, Huzhou Central Hospital, Huzhou, Zhejiang Province, 
      China.
FAU - He, Fengying
AU  - He F
AD  - Department of Ophthalmology, Huzhou Central Hospital, Huzhou, Zhejiang Province, 
      China; Hefengying_666@163.com.
FAU - Wu, Liping
AU  - Wu L
AD  - Department of Ophthalmology, Huzhou Central Hospital, Huzhou, Zhejiang Province, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230101
PL  - Singapore
TA  - Allergol Immunopathol (Madr)
JT  - Allergologia et immunopathologia
JID - 0370073
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Inflammasomes)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Carrier Proteins)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - 0 (NLRX1 protein, human)
RN  - 0 (FUNDC1 protein, human)
SB  - IM
MH  - Humans
MH  - Reactive Oxygen Species/metabolism/pharmacology
MH  - *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Inflammasomes/metabolism/pharmacology
MH  - Hydrogen Peroxide/metabolism/pharmacology
MH  - Retinal Pigment Epithelium/metabolism/pathology
MH  - Phosphorylation
MH  - Interleukin-6/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Oxidative Stress
MH  - *Macular Degeneration/metabolism/pathology
MH  - Carrier Proteins
MH  - Inflammation/pathology
MH  - Autophagy
MH  - Superoxide Dismutase/metabolism/pharmacology
OTO - NOTNLM
OT  - FUNDC1
OT  - Inflammation
OT  - NLRP3 inflammasome
OT  - NLRX1
OT  - age-related macular degeneration
OT  - autophagy
OT  - oxidative stress
COIS- The authors stated that there were no conflicts of interest to disclose.
EDAT- 2023/01/10 06:00
MHDA- 2023/01/11 06:00
CRDT- 2023/01/09 01:53
PHST- 2022/08/30 00:00 [received]
PHST- 2022/11/04 00:00 [accepted]
PHST- 2023/01/09 01:53 [entrez]
PHST- 2023/01/10 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
AID - 10.15586/aei.v51i1.766 [doi]
PST - epublish
SO  - Allergol Immunopathol (Madr). 2023 Jan 1;51(1):177-186. doi: 
      10.15586/aei.v51i1.766. eCollection 2023.