Pigment-epithelium-derived factor (PEDF) occurs at a physiologically relevant concentration in human blood: purification and characterization.
Pigment epithelium-derived factor (PEDF) inhibits the formation of blood vessels in the eye by inducing apotosis in actively dividing endothelial cells. The activity of PEDF equals or supersedes that of other anti-angiogenic factors, including angiostatin, endostatin and thrombospondin-1. In addition, PEDF has the potential to promote the survival of neurons and affect their differentiation. Here we show that PEDF is present in plasma at a concentration of approx. 100 nM (5 microg/ml) or twice the level required to inhibit aberrant blood-vessel growth in the eye. Thus the systemic delivery of PEDF has the potential to affect angiogenesis or neurotrophic processes throughout the body, significantly expanding the putative physiological role of the protein. A complete map of all post-translational modifications revealed that authentic plasma PEDF carries an N-terminal pyroglutamate blocking group and an N-linked glycan at position Asn266. The pyroglutamate residue may regulate the activity of PEDF analogously to the manner in which it regulates thyrotropin-releasing hormone.
Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus C, Denmark.
Steen V
SV
Petersen
Zuzana
Z
Valnickova
Jan J
JJ
Enghild
D000478:Alkylation; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000502:physiology; D002846:Chromatography, Affinity; D024042:Collagen Type I / Q000302:isolation & purification; D003545:Cysteine; D015180:Electrophoresis, Gel, Two-Dimensional; D005136:Eye Proteins; D006801:Humans; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000097:blood / Q000302:isolation & purification / Q000502:physiology; D009414:Nerve Growth Factors; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification; D011506:Proteins / Q000302:isolation & purification / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D012867:Skin / Q000737:chemistry; D000099174:Pigment Epithelium-Derived Factor
D024042:Collagen Type I; D003545:Cysteine; D005136:Eye Proteins; D020932:Nerve Growth Factor; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011134:Polysaccharides; D011506:Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor