Prolactin/growth hormone-derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis.
Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical. We have previously shown that 16-kDa fragments of the human prolactin/growth hormone (PRL/GH) family members are potent angiogenesis inhibitors. Here, we demonstrate that all these fragments possess a 14-aa sequence having the characteristics of a tilted peptide. The tilted peptides of human prolactin and human growth hormone induce endothelial cell apoptosis, inhibit endothelial cell proliferation, and inhibit capillary formation both in vitro and in vivo. These antiangiogenic effects are abolished when the peptides' hydrophobicity gradient is altered by mutation. We further demonstrate that the well known tilted peptides of simian immunodeficiency virus gp32 and Alzheimer's beta-amyloid peptide are also angiogenesis inhibitors. Taken together, these results point to a potential new role for tilted peptides in regulating angiogenesis.
Nguyen
Ngoc-Quynh-Nhu
NQ
Laboratory of Molecular Biology and Genetic Engineering, Center of Biomedical Integrative Genoproteomics, University of Liège, B-4000 Liège, Belgium.
Tabruyn
Sebastien P
SP
Lins
Laurence
L
Lion
Michelle
M
Cornet
Anne M
AM
Lair
Florence
F
Rentier-Delrue
Francoise
F
Brasseur
Robert
R
Martial
Joseph A
JA
Struman
Ingrid
I
D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000737:chemistry*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002417:Cattle; D049109:Cell Proliferation; D002642:Chick Embryo; D042783:Endothelial Cells / Q000166:cytology; D015686:Gene Products, env / Q000737:chemistry; D013006:Growth Hormone / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000378:metabolism; D008561:Membrane Fusion / Q000502:physiology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D050505:Mutant Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry*; D011388:Prolactin / Q000737:chemistry*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry; D014760:Viral Fusion Proteins / Q000737:chemistry
D016229:Amyloid beta-Peptides; D020533:Angiogenesis Inhibitors; D015686:Gene Products, env; D008081:Liposomes; D050505:Mutant Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D014760:Viral Fusion Proteins; C059580:transmembrane protein, Simian immunodeficiency virus; D011388:Prolactin; D013006:Growth Hormone