PMID- 36552548
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221225
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 12
DP  - 2022 Nov 26
TI  - Palmitic Acid Induced a Long-Lasting Lipotoxic Insult in Human Retinal Pigment 
      Epithelial Cells, which Is Partially Counteracted by TRAIL.
LID - 10.3390/antiox11122340 [doi]
LID - 2340
AB  - Hyperglycaemia and increased circulating saturated fatty acids are key metabolic 
      features of type 2 diabetes mellitus (T2DM) that contribute to diabetic 
      retinopathy pathogenesis. Contrarily, tumor necrosis factor (TNF)-related 
      apoptosis-inducing ligand (TRAIL) has been shown to improve or prevent T2DM. This 
      study aimed at investigating the effect of TRAIL in an in vitro model of human 
      retinal pigment epithelium: the ARPE-19 cell line, treated with palmitic acid 
      (PA) in the presence of high glucose concentration. PA caused a drop in cellular 
      metabolic activity and cell viability as well as an increase in apoptosis rates, 
      which were paralleled by an upregulation of reactive oxygen species (ROS) 
      generation as well as mitochondrial fragmentation. Despite ARPE-19 cells 
      expressing TRAIL-R2 at the cell surface, TRAIL failed to counteract the cytotoxic 
      effects of PA. However, when TRAIL was used alongside PA and then removed or used 
      alone following PA challenge, it partially attenuated PA-induced lipotoxicity. 
      This effect of TRAIL appeared to rely upon the modulation of inflammation and ROS 
      production. Thus, TRAIL exerted a trophic effect on ARPE-19 cells, which became 
      evident only when the lipotoxic insult was removed. Nevertheless, whether 
      recombinant TRAIL might have a therapeutic potential for the treatment of 
      diabetic retinopathy requires further investigation.
FAU - Sergi, Domenico
AU  - Sergi D
AUID- ORCID: 0000-0002-3001-410X
AD  - Department of Translational Medicine, University of Ferrara, 44121 Ferrara, 
      Italy.
FAU - Zauli, Enrico
AU  - Zauli E
AD  - Department of Translational Medicine, University of Ferrara, 44121 Ferrara, 
      Italy.
FAU - Casciano, Fabio
AU  - Casciano F
AUID- ORCID: 0000-0002-6431-3335
AD  - Department of Translational Medicine and LTTA Centre, University of Ferrara, 
      44121 Ferrara, Italy.
AD  - Interdepartmental Research Center for the Study of Multiple Sclerosis and 
      Inflammatory and Degenerative Diseases of the Nervous System, University of 
      Ferrara, 44121 Ferrara, Italy.
FAU - Secchiero, Paola
AU  - Secchiero P
AD  - Department of Translational Medicine and LTTA Centre, University of Ferrara, 
      44121 Ferrara, Italy.
FAU - Zauli, Giorgio
AU  - Zauli G
AD  - King Khaled Eye Specialistic Hospital, Riyadh 11462, Saudi Arabia.
FAU - Fields, Matteo
AU  - Fields M
AD  - Department of Translational Medicine, University of Ferrara, 44121 Ferrara, 
      Italy.
FAU - Melloni, Elisabetta
AU  - Melloni E
AUID- ORCID: 0000-0002-7829-0824
AD  - Department of Translational Medicine and LTTA Centre, University of Ferrara, 
      44121 Ferrara, Italy.
LA  - eng
GR  - FAR and FIRD/University of Ferrara/
PT  - Journal Article
DEP - 20221126
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC9774631
OTO - NOTNLM
OT  - ARPE-19
OT  - TRAIL
OT  - lipotoxicity
OT  - palmitic acid
OT  - retinal pigment epithelial cells
OT  - type 2 diabetes mellitus
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/24 06:01
PMCR- 2022/11/26
CRDT- 2022/12/23 01:16
PHST- 2022/10/14 00:00 [received]
PHST- 2022/11/15 00:00 [revised]
PHST- 2022/11/22 00:00 [accepted]
PHST- 2022/12/23 01:16 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/24 06:01 [medline]
PHST- 2022/11/26 00:00 [pmc-release]
AID - antiox11122340 [pii]
AID - antioxidants-11-02340 [pii]
AID - 10.3390/antiox11122340 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2022 Nov 26;11(12):2340. doi: 10.3390/antiox11122340.