Peroxisome Proliferator-Activated Receptor Alpha (PPARα; NR1C1)

Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined.

[Provided by RefSeq, Jul 2008]

NRR Pathway

pparalpha-pathway

Peroxisome Proliferator-Activated Receptor Alpha Structure

mmdbsrv-6_100

(From Structure)

Link

 

(From Aceview)

There are 294 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (Arteriosclerosis; Body Weight; Breast Neoplasms; Cardiovascular Diseases; Cholesterol, HDL/blood*; Coronary Disease; Cystic fibrosis; Diabetes mellitus, type 2; Diabetic Angiopathies; Drug Toxicity and 15 others), proposed to participate in pathways (Adipocytokine signaling pathway, Basic mechanism of action of PPARa PPARb(d) and PPARg and effects on gene expression, Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha), PPAR signaling pathway, Regulation of PGC-1a, Toll-Like Receptor Pathway) and processes (epidermis development, lipoprotein metabolic process, negative regulation of appetite, negative regulation of blood pressure, positive regulation of fatty acid oxidation and 6 others). Proteins are expected to have molecular functions (ligand-regulated transcription factor activity, metal ion binding, protein domain specific binding, sequence-specific DNA binding and 3 others) and to localize in nucleus. Putative protein interactors have been described (AIP, AKAP13, CEP350, CHD9, DAP3, DUT, EP300, FABP1, GADD45A, GADD45B and 25 others). 

(From HuGENavigator)

  • Diabetes Mellitus, Type 2  
  • Coronary Artery Disease  
  • Obesity  
  • Cardiovascular Diseases  
  • Coronary Disease  
  • Alzheimer Disease  
  • Atherosclerosis  
  • Dyslipidemias  
  • Disease Progression  
  • Fatty Liver  
  • Hyperlipidemias  
  • Hypertension  
  • Inflammation  
  • Insulin Resistance  
  • Hypertriglyceridemia  
  • Diabetes Mellitus  
  • Metabolic Syndrome X  
  • Myocardial Infarction  
  • Edema  
  • Body Weight  
  • Fetal Membranes, Premature Rupture  
  • Diabetes Complications  
  • Arteriosclerosis  
  • Chorioamnionitis  
  • Hypertrophy, Left Ventricular  
  • Hypercholesterolemia  
  • Glucose Metabolism Disorders  
  • Hepatitis C, Chronic  
  • Obesity, Morbid  
  • Hyperlipidemia, Familial Combined  
  • Myocardial Ischemia  
  • Neoplasms  
  • Multiple Sclerosis  
  • Obstetric Labor, Premature  
  • Osteoporosis  
  • Ovarian Neoplasms  
  • Peripheral Vascular Diseases  
  • Polycystic Ovary Syndrome  
  • Pre-Eclampsia  
  • Premature Birth  
  • Prostatic Neoplasms  
  • Psoriasis  
  • Psychomotor Performance  
  • Radiation Injuries  
  • Radiation Pneumonitis  
  • Rhinitis, Allergic, Seasonal  
  • Stroke  
  • Syndrome  
  • Task Performance and Analysis  
  • Thrombosis  
  • Tobacco Use Disorder  
  • Ventricular Dysfunction, Left  
  • HIV Seropositivity  
  • HIV-Associated Lipodystrophy Syndrome  
  • Hyperglycemia  
  • Glomerulonephritis, IGA  
  • Kidney Failure, Chronic  
  • Liver Cirrhosis  
  • Liver Neoplasms  
  • Lung Neoplasms  
  • Metabolic Diseases  
  • Diabetes, Gestational  
  • Diabetic Angiopathies  
  • Diabetic Cardiomyopathies  
  • Drug Toxicity  
  • Esophageal Neoplasms  
  • Esophagitis  
  • Brain Ischemia  
  • Breast Neoplasms  
  • Calcinosis  
  • Carcinoma, Hepatocellular  
  • Carcinoma, Non-Small-Cell Lung  
  • Carcinoma, Squamous Cell  
  • Arterial Occlusive Diseases  
  • Adenocarcinoma  
  • Altitude Sickness  
  • Birth Weight  
  • Carotid Stenosis  
  • Coronary Restenosis  
  • Coronary Stenosis  
  • Dementia 

Assay Kits and Services are available from INDIGO Biosciences.

Kits are offered in different assay formats to accommodate researchers’ needs: 3x 32, 1x 96, and 1x 384 assay formats for screening small numbers of test compounds, as well as custom bulk reagents for HTS applications. Assay systems are all inclusive, providing reporter cells, optimized growth media, media for diluting test compounds, a positive-control agonist, luciferase detection reagent, a white assay plate, a detailed protocol, and a protocol quick guide. All kits are shipped on dry ice.

PPARα Reporter Cells are prepared using INDIGO’s proprietary CryoMite™ process. This cryo-preservation method yields high cell viability post-thaw, and provides the convenience of immediately dispensing healthy, division-competent reporter cells into assay plates. There is no need for intermediate spin-and-wash steps, viability determinations, or cell titer adjustments.

The principle application of this assay product is in the screening of test samples to quantify functional activities, either agonist or antagonist, that they may exert against the peroxisome proliferator-activated receptor. This kit product is an all-inclusive assay system that includes, in addition to PPARα Reporter Cells, two optimized media for use during cell culture and (optionally) in diluting the test samples, a reference agonist, Luciferase Detection Reagent, a cell culture-ready assay plate, and a detailed protocol.

hPPAR; NR1C1y

(From Aceview)

The gene contains 20 distinct gt-ag introns. Transcription produces 16 different mRNAs, 12 alternatively spliced variants and 4 unspliced forms. There are 5 probable alternative promotors, 6 non overlapping alternative last exons and 2 validated alternative polyadenylation sites (see thediagram). The mRNAs appear to differ by truncation of the 5′ end, truncation of the 3′ end, presence or absence of 4 cassette exons, overlapping exons with different boundaries. 2644 bp of this gene are antisense to spliced gene C22orf40, raising the possibility of regulated alternate expression. 

image-7_med

(From STRINGS)

RXRA, ACOX1, Rxr, NCOA1, PPARGC1A, pirinixic acid, Acox, NCOR1, fibric acid derivative, MED1 (includes EG:19014), NCOA6, 8(S)-hydroxyeicosatetraenoic acid, fatty acid, GW2331, arachidonic acid

(From KEGG)

  • choline fenofibrate
  • clofibrate
  • docosahexaenoic acid
  • fenofibrate
  • gemfibrozil
  • NS-220
  • tesaglitazar

(From BioGPS)

206870_at_med