Enzyme association with PPARgamma: evidence of a new role for 15-lipoxygenase type 2.
Fatty acids have historically important structural roles in contributing to epidermal barrier function and therefore cutaneous health. Their metabolism to bioactive compounds is often up-regulated in response to cutaneous toxins thus providing them with functional roles. Some metabolites of arachidonic acid, such as 15S-hydroxyeicosatetraenoic acid (HETE), also serve functional roles as direct ligands for peroxisome proliferator activated receptors (PPARs). 15S-HETE, produced by 15-lipoxygenase type 2 (15-LOX-2), is an endogenous ligand for PPARgamma. This report demonstrates epidermal keratinocyte expression of both 15-LOX-2 and PPARgamma and provides evidence for a relationship beyond that of ligand-producer and -user, namely in vivo association of the two proteins at the molecular level making the enzyme a candidate nuclear receptor coregulator. Such close physical approximation of the 15S-HETE-producing enzyme and PPARgamma could potentiate the receptor response to a short-lived ligand. 15-LOX-2 may exemplify a class of enzymatically active nuclear receptor coactivator proteins distinct from those previously described but sharing their ability to promote expression from nuclear receptor-regulated promoters.
Flores
Anthony M
AM
Department of Pharmaceutical Sciences, 372 Fairfield Road, U-2092, University of Connecticut, Storrs, CT 06269, USA.
Li
Lu
L
McHugh
Nora G
NG
Aneskievich
Brian J
BJ
D000595:Amino Acid Sequence; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
D047495:PPAR gamma; D001093:Arachidonate 15-Lipoxygenase