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Inhibitory activity of the peptides derived from buffalo prolactin on angiogenesis

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Abstract

The peptide fragments obtained by cathepsin digestion of purified buffalo prolactin (buPRL) monomer have been characterized using SDS-PAGE and FPLC with regard to size and pI. Their antiangiogenic activity was tested in chick embryo chorioallantoic membrane (CAM) assay and the human endothelial cells wound healing assay. Antiangiogenic activity was observed in cathepsin-cleaved fragments from buPRL. Further, a peptide sequence 45A-46Q-47G-48K-49G-50F-51I-52T-53M-54A-55L-56N-57S-58C, which matched with human somatostatin (hSST), a known antiangiogenic factor, was located in the second loop between the first and second α-helices in the three-dimensional structure of buPRL, obtained by homology modelling. The synthetic peptide matching with SST sequence was found to exhibit antiangiogenic activity in both in vitro and ex vivo assays. It was also observed that all the peptides related to buPRL could antagonize the vascular endothelial growth factor (VEGF) and bradykinin (BK)-dependent production of endothelial nitric oxide (NO), which is a pre-requisite for endothelial tube formation. It is concluded therefore that an internal sequence in buPRL and peptide fragments derived from cathepsin-digested buPRL exhibit antiangiogenic activities.

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Abbreviations

BBBE:

bovine brain basal endothelial

BK:

bradykinin

buPRL:

buffalo prolactin

BUVE:

bovine umbilical vein endothelial

CAM:

chorioallantoic membrane

CD:

cathepsin D

DAF-FM:

diaminofluorescein

eNOS:

endothelial NOS

FGF:

fibroblast growth factor

FPLC:

fast-performance liquid chromatography

GH:

growth hormone

HRP:

horseradish peroxidase

hSST:

human somatostatin

HUVE:

human umbilical vein endothelial

KS:

Kaposi sarcoma

NOS:

NO synthase

rPRL:

rat prolactin

SST:

somatostatin

VEGF:

vascular endothelial growth factor

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Acknowledgements

The financial assistance provided by Indian Council of Cultural Relations and University of Delhi through ‘R&D Doctoral Research Programme’ support scheme is highly acknowledged.

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Authors and Affiliations

  1. Hormone Research Laboratory, Department of Zoology, University of Delhi, Delhi, India

    Jaeok Lee & Kambadur Muralidhar

  2. AU-KBC Research Centre, MIT Campus, Anna University, Chennai, India

    Syamantak Majumder & Suvro Chatterjee

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  1. Jaeok Lee
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  2. Syamantak Majumder
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  3. Suvro Chatterjee
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  4. Kambadur Muralidhar
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Correspondence to Kambadur Muralidhar.

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Corresponding editor: Maneesha Inamdar

[Lee J, Majumder S, Chatterjee S and Muralidhar K 2011 Inhibitory activity of the peptides derived from buffalo prolactin on angiogenesis. J. Biosci. 36 341–354] DOI doi:10.1007/s12038-011-9073-6

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Lee, J., Majumder, S., Chatterjee, S. et al. Inhibitory activity of the peptides derived from buffalo prolactin on angiogenesis. J Biosci 36, 341–354 (2011). https://doi.org/10.1007/s12038-011-9073-6

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