PMID- 23723389
OWN - NLM
STAT- MEDLINE
DCOM- 20140224
LR  - 20240420
IS  - 1539-7262 (Electronic)
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 54
IP  - 8
DP  - 2013 Aug
TI  - Retinoid X receptor activation is essential for docosahexaenoic acid protection 
      of retina photoreceptors.
PG  - 2236-2246
LID - S0022-2275(20)37539-8 [pii]
LID - 10.1194/jlr.M039040 [doi]
AB  - We have established that docosahexaenoic acid (DHA), the major polyunsaturated 
      fatty acid in the retina, promotes survival of rat retina photoreceptors during 
      early development in vitro and upon oxidative stress by activating the ERK/MAPK 
      signaling pathway. Here we have investigated whether DHA turns on this pathway 
      through activation of retinoid X receptors (RXRs) or by inducing tyrosine kinase 
      (Trk) receptor activation. We also evaluated whether DHA release from 
      phospholipids was required for its protective effect. Addition of RXR antagonists 
      (HX531, PA452) to rat retinal neuronal cultures inhibited DHA protection during 
      early development in vitro and upon oxidative stress induced with Paraquat or 
      H2O2. In contrast, the Trk inhibitor K252a did not affect DHA prevention of 
      photoreceptor apoptosis. These results imply that activation of RXRs was required 
      for DHA protection whereas Trk receptors were not involved in this protection. 
      Pretreatment with 4-bromoenol lactone, a phospholipase A2 inhibitor, blocked DHA 
      prevention of oxidative stress-induced apoptosis of photoreceptors. It is 
      noteworthy that RXR agonists (HX630, PA024) also rescued photoreceptors from 
      H2O2-induced apoptosis. These results provide the first evidence that activation 
      of RXRs prevents photoreceptor apoptosis and suggest that DHA is first released 
      from phospholipids and then activates RXRs to promote the survival of 
      photoreceptors.
FAU - German, Olga L
AU  - German OL
AD  - Instituto de Investigaciones Bioquimicas de Bahia Blanca, Universidad Nacional 
      del Sur-CONICET, Buenos Aires, Argentina.
FAU - Monaco, Sandra
AU  - Monaco S
AD  - Instituto de Investigaciones Bioquimicas de Bahia Blanca, Universidad Nacional 
      del Sur-CONICET, Buenos Aires, Argentina.
FAU - Agnolazza, Daniela L
AU  - Agnolazza DL
AD  - Instituto de Investigaciones Bioquimicas de Bahia Blanca, Universidad Nacional 
      del Sur-CONICET, Buenos Aires, Argentina.
FAU - Rotstein, Nora P
AU  - Rotstein NP
AD  - Instituto de Investigaciones Bioquimicas de Bahia Blanca, Universidad Nacional 
      del Sur-CONICET, Buenos Aires, Argentina. Electronic address: 
      inpoliti@criba.edu.ar.
FAU - Politi, Luis E
AU  - Politi LE
AD  - Instituto de Investigaciones Bioquimicas de Bahia Blanca, Universidad Nacional 
      del Sur-CONICET, Buenos Aires, Argentina. Electronic address: 
      inrotste@criba.edu.ar.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130530
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Benzoates)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (diazepinylbenzoic acid)
RN  - 25167-62-8 (Docosahexaenoic Acids)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Benzoates/pharmacology
MH  - Biphenyl Compounds/pharmacology
MH  - Cell Survival/drug effects
MH  - Docosahexaenoic Acids/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Retinal Rod Photoreceptor Cells/cytology/*drug effects/metabolism
MH  - Retinoid X Receptors/antagonists & inhibitors/*metabolism
MH  - Structure-Activity Relationship
PMC - PMC3708373
OTO - NOTNLM
OT  - RXR agonists
OT  - apoptosis
OT  - oxidative damage
OT  - photoreceptor survival
EDAT- 2013/06/01 06:00
MHDA- 2014/02/25 06:00
PMCR- 2014/08/01
CRDT- 2013/06/01 06:00
PHST- 2013/06/01 06:00 [entrez]
PHST- 2013/06/01 06:00 [pubmed]
PHST- 2014/02/25 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - S0022-2275(20)37539-8 [pii]
AID - m039040 [pii]
AID - 10.1194/jlr.M039040 [doi]
PST - ppublish
SO  - J Lipid Res. 2013 Aug;54(8):2236-2246. doi: 10.1194/jlr.M039040. Epub 2013 May 
      30.