Peroxisome proliferator-activated receptor
Peroxisome proliferator-activated receptors (PPARs) are a group of receptor_(proteomics)nuclear receptor]] isoforms that exist accross biology. Originally identified in Xenopus frogs as receptors that induce the proliferation of peroxisomes, they are intimately connected to the cellular metabolism and cell differentiation. They are transcription factors.
Nomenclature
Three types of PPARs have been identified: alpha, gamma and delta (beta).
- α (alpha) - expressed in kidney, heart, muscle, adipose tissue, and others.
- γ (gamma) - although transcribed by the same gene, this PPAR exists in two forms:
- γ1 - expressed in heart, muscle, colon, kidney, pancreas and spleen.
- γ2 - expressed mainly in adipose tissue (30 aminoacids longer)
- δ (delta) - expressed in many tissues but markedly in brain, adipose tissue and skin.
What happened to PPARß (beta)?
After this gene was identified in humans in 1992, it turned out to be identical to the PPARß (beta) previously described in other animals (Xenopus). The name PPARd is generally used to the exclusion of PPARß.
Physiological function
All PPARs dimerize with the retinoid X-receptor (RXR) and bind to specific regions on the DNA, termed PPREs (peroxisome proliferator response elements). The DNA consensus sequence is AGGTCAXAGGTCA with X being a random nucleotide. Generally, this sequence occurs in the promotor region of a gene, and when the PPAR is activated, transcription is increased.
Genetics
- To follow
PPAR-alpha
PPAR-alpha is the main target of fibrate drugs, a class of amphipathic carboxylic acids (clofibrate, gemfibrozil and others). They are used in cholesterol disorders (generally as an adjunctive to statins) and disorders that feature high triglycerides.
PPAR-gamma
PPAR-gamma is the main target of the drug class of thiazolidinediones, used in diabetes mellitus and other diseases that feature insulin resistance.
See also
Sources
- Berger J, Moller DE. The mechanism of action of PPARs. Annu Med Rev 2002;53:409-35. PMID ...
External links
- PPAR resource (Penn State University).