[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Nguyen, Ngoc-Quynh-Nhu ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Tabruyn, Sébastien ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Lins, Laurence ; Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér.
Lion, Michelle ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Cornet, Anne ; Université de Liège - ULiège > Département de morphologie et pathologie > Pathologie spéciale et autopsies
Lair, Florence
Rentier-Delrue, Françoise ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Brasseur, Robert ; Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie moléc. et numér.
Martial, Joseph ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Struman, Ingrid ; Université de Liège - ULiège > Département des sciences de la vie > Biologie et génétique moléculaire
Language :
English
Title :
Prolactin/growth hormone-derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis
Publication date :
2006
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Maeshima Y, Yerramalla UL, Dhanabal M, Holthaus KA, Barbashov S, Kharbanda S, Reimer C, Manfredi M, Dickerson WM, Kalluri R (2001) J Biol Chem 276:31959-31968.
D'Angelo G, Struman I, Martial JA, Weiner RI (1995) Proc Natl Acad Sci USA 92:6374-6378.
D'Angelo G, Martini JF, Iiri T, Fantl WJ, Martial JA, Weiner RI (1999) Mol Endocrinol 13:692-704.
Lee H, Struman I, Clapp C, Martial JA, Weiner RI (1998) Endocrinology 139:3696-3703.
Martini JF, Piot C, Humeau LM, Struman I, Martial JA, Weiner RI (2000) Mol Endocrinol 14:1536-1549.
Tabruyn SP, Sorlet CM, Rentier-Delrue F, Bours V, Weiner RI, Martial JA, Struman I (2003) Mol Endocrinol 17:1815-1823.