Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists

We describe the cloning, characterization, and tissue distribution of the two human peroxisome proliferator activated receptor isoforms hPPARgamma2 and hPPARgamma1. In cotransfection assays the two isoforms were activated to approximately the same extent by known PPARgamma activators. Human PPARgamm...

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Bibliographic Details
Published in:The Journal of biological chemistry 1997-03, Vol.272 (12), p.8071-8076
Main Authors: Mukherjee, R, Jow, L, Croston, G E, Paterniti, Jr, J R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Biopolymers
Blotting, Northern
Cloning, Molecular
DNA, Complementary
Humans
Isomerism
Molecular Sequence Data
Myocardium - metabolism
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Retinoic Acid - agonists
Receptors, Retinoic Acid - antagonists & inhibitors
Retinoid X Receptors
Transcription Factors - agonists
Transcription Factors - antagonists & inhibitors
Transcription Factors - metabolism
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Summary:We describe the cloning, characterization, and tissue distribution of the two human peroxisome proliferator activated receptor isoforms hPPARgamma2 and hPPARgamma1. In cotransfection assays the two isoforms were activated to approximately the same extent by known PPARgamma activators. Human PPARgamma binds to DNA as a heterodimer with the retinoid X receptor (RXR). This heterodimer was activated by both RXR agonists and antagonists and the addition of PPARgamma ligands with retinoids resulted in greater than additive activation. Such heterodimer-selective modulators may have a role in the treatment of PPARgamma/RXR-modulated diseases like diabetes. Northern blot analysis indicated the presence of PPARgamma in skeletal muscle, and a sensitive RNase protection assay confirmed the presence of only PPARgamma1 in muscle that was not solely due to fat contamination. However, both PPARgamma1 and PPARgamma2 RNA were detected in fat, and the ratio of PPARgamma1 to PPARgamma2 RNA varied in different individuals. The presence of tissue-specific distribution of isoforms and the variable ratio of PPARgamma1 to PPARgamma2 raised the possibility that isoform expression may be modulated in disease states like non-insulin-dependent diabetes mellitus. Interestingly, a third protected band was detected with fat RNA indicating the possible existence of a third human PPARgamma isoform.
ISSN:0021-9258