PMID- 11471659
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20191105
IS  - 0910-8327 (Print)
IS  - 0910-8327 (Linking)
VI  - 15
IP  - 4
DP  - 2000
TI  - A nuclear complex containing PPARalpha/RXRalpha is markedly downregulated in the 
      hypertrophied rat left ventricular myocardium with normal systolic function.
PG  - 191-6
AB  - The expression of genes encoding fatty acid utilization enzymes is coordinately 
      downregulated during the development of cardiac hypertrophy and failure. However, 
      molecular mechanisms that mediate this downregulation are unknown. Peroxisome 
      proliferator-activated receptor (PPAR) response elements (PPREs) have been 
      identified in promoters of many genes involved in fatty acid utilization, where 
      they function as positive regulatory elements. PPARs bind to PPREs as 
      heterodimers with retinoid X receptors (RXRs). Primary cardiac myocytes from 
      neonatal rats were transfected with a reporter construct driven by the C promoter 
      of rat acyl-coenzyme A synthetase (ACS) gene. Stimulation with phenylephrine, a 
      potent inducer of hypertrophy, markedly downregulated the activity of this 
      promoter. By use of electrophoretic mobility-shift assays (EMSAs) using PPRE in 
      the rat ACS promoter as a probe, we found a sequence-specific protein-DNA complex 
      in the nuclear extract from adult rat left ventricular (LV) myocardium. 
      Supershift experiments revealed that this complex was immunoreactive for 
      PPARalpha and RXRalpha. We compared the activity of this complex in LV nuclear 
      extracts from Dahl salt-sensitive rats (DSs) with hypertension and control 
      age-matched Dahl salt-resistant rats (DRs). Even at the stage of concentric LV 
      hypertrophy with normal systolic function, the activity of the band was markedly 
      diminished in DSs compared with DRs. However, immunoblot analyses showed no 
      difference in LV expression levels of PPARalpha or RXRalpha between DSs and DRs. 
      These findings indicate that a nuclear complex of PPARalpha/RXRalpha is present 
      in adult rat LV and is markedly downregulated in the hypertrophied LV from DS 
      rats, which may account for the loss of transcriptional activation. The 
      downregulation of this complex precedes LV systolic dysfunction and is mediated 
      at the posttranslational levels.
FAU - Kanda, H
AU  - Kanda H
AD  - Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto 
      University, Japan.
FAU - Nohara, R
AU  - Nohara R
FAU - Hasegawa, K
AU  - Hasegawa K
FAU - Kishimoto, C
AU  - Kishimoto C
FAU - Sasayama, S
AU  - Sasayama S
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Heart Vessels
JT  - Heart and vessels
JID - 8511258
RN  - 0 (Fatty Acids)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Coenzyme A Ligases/metabolism
MH  - *Down-Regulation
MH  - Fatty Acids/metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - Hypertrophy, Left Ventricular/*physiopathology
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Rats, Inbred Dahl
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factors/*metabolism
EDAT- 2001/07/27 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/07/27 10:00
PHST- 2001/07/27 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/07/27 10:00 [entrez]
AID - 10.1007/s003800070022 [doi]
PST - ppublish
SO  - Heart Vessels. 2000;15(4):191-6. doi: 10.1007/s003800070022.