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Abstract Title:

Phenolic Compounds fromRegulate Viability and Apoptosis of Pancreaticβ-Cells Possibly via SERCA Activity.

Abstract Source:

ACS Med Chem Lett. 2020 May 14 ;11(5):1006-1013. Epub 2020 Mar 26. PMID: 32435418

Abstract Author(s):

Vladimir Heger, Barbora Benesova, Jana Viskupicova, Magdalena Majekova, Zoofishan Zoofishan, Attila Hunyadi, Lubica Horakova

Article Affiliation:

Vladimir Heger

Abstract:

The ability of phenolic compounds fromto modulate sarco-endoplasmic Ca-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 Carelease. 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.

Study Type : In Vitro Study

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