title: Peptides derived from the copper-binding region of lysyl oxidase exhibit antiangiogeneic properties by inhibiting enzyme activity: an in vitro study.
abstract: Despite the rigorous research on abnormal angiogenesis, there is a persistent need for the development of new and efficient therapies against angiogenesis-related diseases. The role of Lysyl oxidase (LOX) in angiogenesis and cancer has been established in prior studies. Copper is known to induce the synthesis of LOX, and hence regulates its activity. Hypoxia-induced metastasis is dependent on LOX expression and activity. It has been believed that the inhibition of LOX would be a therapeutic strategy to inhibit angiogenesis. To explore this, we designed peptides (M peptides) from the copper-binding region of LOX and hypothesized them to modulate LOX. The peptides were characterized, and their copper-binding ability was confirmed by mass spectrometry. The M peptides were found to reduce the levels of intracellular copper when the cells were co-treated with copper. The peptides showed promising effect on aortic LOX, recombinant human LOX and LOX produced by human umbilical vein endothelial cells (HUVECs). The study also explores the effect of these peptides on copper and hypoxia-stimulated angiogenic response in HUVECs. It was found that the M peptides inhibited copper/hypoxia-induced LOX activity and inhibited stimulated HUVEC tube formation and migration. This clearly indicated the potential of M peptides in inhibiting angiogenesis, highlighting their role in the formulation of drugs for the same.
authors.affiliation: R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Medical Research Foundation, Chennai, Tamil Nadu, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Mohankumar
authors.forename: Bhuvanasundar
authors.initials: B
authors.lastname: Renganathan
authors.forename: Coral
authors.initials: C
authors.lastname: Karunakaran
authors.forename: Subbulakshmi
authors.initials: S
authors.lastname: Chidambaram
authors.forename: Sulochana
authors.initials: S
authors.lastname: Konerirajapuram Natarajan
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001665:Binding Sites; D015687:Cell Hypoxia; D002465:Cell Movement / Q000187:drug effects; D003300:Copper / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017433:Protein Structure, Secondary; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D012333:RNA, Messenger; D011994:Recombinant Proteins; D006639:Histidine; D003300:Copper; D008249:Protein-Lysine 6-Oxidase
keywords: antiangiogenic peptides; cell migration; lysyl oxidase; lysyl oxidase activity; mass spectrometry; tube formation