PMID- 22718360
OWN - NLM
STAT- MEDLINE
DCOM- 20130124
LR  - 20211021
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 228
IP  - 2
DP  - 2013 Feb
TI  - Retinoic acid protects cardiomyocytes from high glucose-induced apoptosis through 
      inhibition of NF-kappaB signaling pathway.
PG  - 380-92
LID - 10.1002/jcp.24142 [doi]
AB  - We have previously shown that retinoic acid (RA) has protective effects on high 
      glucose (HG)-induced cardiomyocyte apoptosis. To further elucidate the molecular 
      mechanisms of RA effects, we determined the interaction between nuclear factor 
      (NF)-kappaB and RA signaling. HG induced a sustained phosphorylation of IKK/IkappaBalpha and 
      transcriptional activation of NF-kappaB in cardiomyocytes. Activated NF-kappaB signaling 
      has an important role in HG-induced cardiomyocyte apoptosis and gene expression 
      of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, and monocyte 
      chemoattractant protein-1 (MCP-1). All-trans RA (ATRA) and LGD1069, through 
      activation of RAR/RXR-mediated signaling, inhibited the HG-mediated effects in 
      cardiomyocytes. The inhibitory effect of RA on NF-kappaB activation was mediated 
      through inhibition of IKK/IkappaBalpha phosphorylation. ATRA and LGD1069 treatment 
      promoted protein phosphatase 2A (PP2A) activity, which was significantly 
      suppressed by HG stimulation. The RA effects on IKK and IkappaBalpha were blocked by 
      okadaic acid or silencing the expression of PP2Ac-subunit, indicating that the 
      inhibitory effect of RA on NF-kappaB is regulated through activation of PP2A and 
      subsequent dephosphorylation of IKK/IkappaBalpha. Moreover, ATRA and LGD1069 reversed the 
      decreased PP2A activity and inhibited the activation of IKK/IkappaBalpha and gene 
      expression of MCP-1, IL-6, and TNF-alpha in the hearts of Zucker diabetic fatty rats. 
      In summary, our findings suggest that the suppressed activation of PP2A 
      contributed to sustained activation of NF-kappaB in HG-stimulated cardiomyocytes; and 
      that the protective effect of RA on hyperglycemia-induced cardiomyocyte apoptosis 
      and inflammatory responses is partially regulated through activation of PP2A and 
      suppression of NF-kappaB-mediated signaling and downstream targets.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Nizamutdinova, Irina T
AU  - Nizamutdinova IT
AD  - Division of Molecular Cardiology, Department of Medicine, College of Medicine, 
      Texas A&M Health Science Center, Temple, Texas 76504, USA.
FAU - Guleria, Rakeshwar S
AU  - Guleria RS
FAU - Singh, Amar B
AU  - Singh AB
FAU - Kendall, Jonathan A Jr
AU  - Kendall JA Jr
FAU - Baker, Kenneth M
AU  - Baker KM
FAU - Pan, Jing
AU  - Pan J
LA  - eng
GR  - R01 HL091902/HL/NHLBI NIH HHS/United States
GR  - 1R01 HL091902/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 5688UTC01R (Tretinoin)
RN  - A61RXM4375 (Bexarotene)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Bexarotene
MH  - Cytokines/biosynthesis
MH  - *Cytoprotection
MH  - Gene Expression Regulation/drug effects
MH  - Hyperglycemia/*complications
MH  - I-kappa B Kinase/metabolism
MH  - Male
MH  - Myocytes, Cardiac/*drug effects
MH  - NF-kappa B/*drug effects
MH  - Phosphorylation
MH  - Protein Phosphatase 2/drug effects
MH  - Rats
MH  - Rats, Zucker
MH  - Signal Transduction/*drug effects
MH  - Tetrahydronaphthalenes/pharmacology
MH  - Tretinoin/*pharmacology
PMC - PMC3470832
MID - NIHMS385058
EDAT- 2012/06/22 06:00
MHDA- 2013/01/25 06:00
PMCR- 2014/02/01
CRDT- 2012/06/22 06:00
PHST- 2012/06/22 06:00 [entrez]
PHST- 2012/06/22 06:00 [pubmed]
PHST- 2013/01/25 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - 10.1002/jcp.24142 [doi]
PST - ppublish
SO  - J Cell Physiol. 2013 Feb;228(2):380-92. doi: 10.1002/jcp.24142.