PMID- 36204727
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221009
IS  - 2405-5808 (Electronic)
IS  - 2405-5808 (Linking)
VI  - 32
DP  - 2022 Dec
TI  - Oxidized low-density lipoprotein causes ribosome reduction and inhibition of 
      protein synthesis in retinal pigment epithelial cells.
PG  - 101345
LID - 10.1016/j.bbrep.2022.101345 [doi]
LID - 101345
AB  - Retinal pigment epithelium (RPE) are specialized multifunctional cells 
      indispensable for maintenance of vision. Dysfunction and death of the RPE cells 
      is implicated in the genesis and progression of age-related macular degeneration 
      (AMD). Oxidative stress and resulting cellular damage plays a critical 
      mechanistic role in AMD pathogenesis. Oxidized low-density lipoprotein (oxLDL), 
      derived from LDL in a pro-oxidative environment, is found adjacent to the RPE as 
      part of drusen, extracellular deposits that are a characteristic clinical feature 
      of AMD. OxLDL is cytotoxic and oxLDL-induced oxidative damage may contribute to 
      functional impairment of the RPE. Therefore, knowledge of how the RPE respond to 
      oxLDL exposure is important to understand the mechanisms underlying RPE 
      dysfunction and death associated with AMD. The objective of this study was to 
      characterize alterations in the RPE proteome triggered by exposure to 
      non-cytotoxic levels of oxLDL. Protein identification and quantification were 
      performed with a high -resolution LC-MS/MS-based proteomics workflow. In total, 
      out of the ca 3000 RPE proteins quantified, oxLDL treatment caused expression 
      changes of 303 proteins. As revealed by protein functional analysis, oxLDL uptake 
      caused a multifaceted molecular response that involved numerous biological 
      pathways. This response included up-regulation of anti-oxidative stress proteins 
      whose expression is mediated by the transcription factor nuclear factor erythroid 
      2-related factor 2 (NRF2), confirming results of transcriptomics studies 
      previously published by us and others. Significantly, and previously unreported, 
      the oxLDL treatment induced down-regulation of ribosomal and translation 
      initiation proteins, and up-regulation of proteins involved in autophagy, thus 
      suggesting that a major cellular mechanism through which the RPE mitigate 
      oxLDL-induced damage involves inhibition of protein synthesis and removal of 
      misfolded proteins.
CI  - (c) 2022 The Authors.
FAU - Giorgianni, Francesco
AU  - Giorgianni F
AD  - Department of Pharmaceutical Sciences, The University of Tennessee Health Science 
      Center, Memphis, TN, USA.
FAU - Beranova-Giorgianni, Sarka
AU  - Beranova-Giorgianni S
AD  - Department of Pharmaceutical Sciences, The University of Tennessee Health Science 
      Center, Memphis, TN, USA.
LA  - eng
PT  - Journal Article
DEP - 20220930
PL  - Netherlands
TA  - Biochem Biophys Rep
JT  - Biochemistry and biophysics reports
JID - 101660999
PMC - PMC9530482
OTO - NOTNLM
OT  - Drusen
OT  - Oxidative stress
OT  - Oxidized LDL
OT  - Proteome
OT  - Proteostasis
OT  - Retinal pigment epithelium
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/10/08 06:00
MHDA- 2022/10/08 06:01
PMCR- 2022/09/30
CRDT- 2022/10/07 03:01
PHST- 2022/04/18 00:00 [received]
PHST- 2022/07/27 00:00 [revised]
PHST- 2022/09/07 00:00 [accepted]
PHST- 2022/10/07 03:01 [entrez]
PHST- 2022/10/08 06:00 [pubmed]
PHST- 2022/10/08 06:01 [medline]
PHST- 2022/09/30 00:00 [pmc-release]
AID - S2405-5808(22)00145-5 [pii]
AID - 101345 [pii]
AID - 10.1016/j.bbrep.2022.101345 [doi]
PST - epublish
SO  - Biochem Biophys Rep. 2022 Sep 30;32:101345. doi: 10.1016/j.bbrep.2022.101345. 
      eCollection 2022 Dec.