A perspective on the modulation of plant and animal two pore channels (TPCs) by the flavonoid naringenin

D Benkerrou; V Minicozzi; A Gradogna; S Milenkovic; I V Bodrenko; M Festa; L Lagostena; L Cornara; A D'Amore; M Ceccarelli; A Filippini; A Carpaneto

doi:10.1016/j.bpc.2019.106246

A perspective on the modulation of plant and animal two pore channels (TPCs) by the flavonoid naringenin

Biophys Chem. 2019 Nov:254:106246. doi: 10.1016/j.bpc.2019.106246. Epub 2019 Aug 9.

Authors

D Benkerrou¹, V Minicozzi², A Gradogna³, S Milenkovic¹, I V Bodrenko⁴, M Festa⁵, L Lagostena³, L Cornara⁶, A D'Amore⁷, M Ceccarelli⁴, A Filippini⁷, A Carpaneto⁸

Affiliations

¹ Department of Physics, University of Cagliari, 09042 Monserrato, Italy.
² INFN and Department of Physics, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Roma, Italy.
³ Institute of Biophysics, National Research Council, Via De Marini 6, 16149 Genova, Italy.
⁴ Department of Physics, University of Cagliari, 09042 Monserrato, Italy; IOM-CNR Unità di Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy.
⁵ Department of Biology, University of Padova, Via U. Bassi 58/b, 35131 Padova, Italy.
⁶ Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Viale Benedetto XV 5, 16132 Genova, Italy.
⁷ Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology, Sapienza University of Rome, 16 Via A. Scarpa, 00161 Rome, Italy.
⁸ Institute of Biophysics, National Research Council, Via De Marini 6, 16149 Genova, Italy; Department of Earth, Environment and Life Sciences (DISTAV), University of Genoa, Viale Benedetto XV 5, 16132 Genova, Italy. Electronic address: [email protected].

PMID: 31426023
DOI: 10.1016/j.bpc.2019.106246

Abstract

The inhibitory effect of the flavonoid naringenin on plant and human Two-Pore Channels (TPCs) was assessed by means of electrophysiological measurements. By acting on human TPC2, naringenin, was able to dampen intracellular calcium responses to VEGF in cultured human endothelial cells and to impair angiogenic activity in VEGF-containing matrigel plugs implanted in mice. Molecular docking predicts selective binding sites for naringenin in the TPC structure, thus suggesting a specific interaction between the flavonoid and the channel.

Keywords: Animal lysosome; Fluorescence; Molecular docking; Patch-clamp; Plant vacuole; TPC channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Calcium / chemistry
Calcium / metabolism
Calcium Channels / chemistry*
Calcium Channels / metabolism
Collagen / chemistry
Drug Combinations
Endothelial Cells / cytology
Endothelial Cells / metabolism
Flavanones / chemistry*
Flavanones / metabolism
Humans
Laminin / chemistry
Mice
Molecular Docking Simulation
Patch-Clamp Techniques
Plant Proteins / antagonists & inhibitors
Plant Proteins / metabolism
Plants / metabolism*
Proteoglycans / chemistry

Substances

Calcium Channels
Drug Combinations
Flavanones
Laminin
Plant Proteins
Proteoglycans
matrigel
Collagen
naringenin
Calcium