ml0c00047_si_001.pdf (216.45 kB)
Phenolic Compounds from Morus nigra Regulate Viability and Apoptosis of Pancreatic β‑Cells Possibly via SERCA Activity
journal contribution
posted on 2020-03-26, 19:34 authored by Vladimir Heger, Barbora Benesova, Jana Viskupicova, Magdalena Majekova, Zoofishan Zoofishan, Attila Hunyadi, Lubica HorakovaThe ability of phenolic compounds
from Morus nigra to modulate sarco-endoplasmic Ca2+-ATPase (SERCA1) activity
was analyzed. Enzyme activity decrease correlated with the binding
energy of agents to SERCA1. Results from theoretical and experimental
approaches were coherent in identifying binding sites to SERCA1. Albanol
A inhibited SERCA1 by immersion in the luminal gate at the site of
Ca2+ release. Kuwanon U exerted an inhibitory effect by
preventing ATP binding in the cytosolic region of SERCA1, and this
was associated with conformational alterations. On the basis of similarities
of SERCA isoforms, the viability of beta-cells containing SERCA2b
was analyzed. Both correlation of viability and negative correlation
of SERCA2b expression with SERCA1 activity were found for agents with
the highest binding energy to SERCA1. The compounds studied may regulate
viability and apoptosis of pancreatic beta-cells via modulation of
SERCA activity. Novel pharmacological interventions in diabetes may
be realized via compounds restoring ER calcium levels.