P 011 - Mycosporine-like amino acid activation of the Keap1-Nrf2 pathway: Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

TY - JOUR

T1 - P 011 - Mycosporine-like amino acid activation of the Keap1-Nrf2 pathway

T2 - Abstracts of the OCC World Congress and Annual SFRR-E Conference 2017 Metabolic Stress and Redox Regulation Berlin, Germany 21-23 June 2017

AU - Gacesa, Ranko

AU - Barlow, David

AU - Dunlap, Walter

AU - Georgakopoulos, Nikolaos

AU - Wells, Geoffrey

AU - Long, Paul

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Oxidative stress is a contributing factor in the progression of numerous pathological conditions including neurodegeneration, cancer and ageing. The Keap1-Nrf2 pathway is a master regulator of oxidative stress: reactive oxygen species are sensed by Keap1 to release Nrf2 for transcriptional activation of protective genes controlled by the nuclear antioxidant response element. We have identified homologs of Nrf2 in early eukaryotes and used virtual screens to predict natural products able to activate Nrf2 by competitive inhibition of Keap1-Nrf2 binding. Mycosporine-like amino acids (MAAs) are water-soluble metabolites produced by taxonomically diverse organisms, particularly marine algae and seaweeds. These compounds absorb UV radiation – thus acting as “primary sunscreens” – and reported also to protect against oxidative damage. We have tested the MAAs, porphyra-334, shinorine, and palythine for in-vitro antioxidant activity using the DPPH free-radical quenching assay and report also their ability to activate the Keap1-Nrf2 pathway using fluorescence polarization and thermal shift assays to detect Keap1 receptor antagonism. Our results demonstrate that shinorine and porphyra-334 are competitive inhibitors of Keap1-Nrf2 binding having potential to protect against UVR via sunscreen absorption and transcriptional activation of endogenous defenses against UV-induced oxidative damage.

AB - Oxidative stress is a contributing factor in the progression of numerous pathological conditions including neurodegeneration, cancer and ageing. The Keap1-Nrf2 pathway is a master regulator of oxidative stress: reactive oxygen species are sensed by Keap1 to release Nrf2 for transcriptional activation of protective genes controlled by the nuclear antioxidant response element. We have identified homologs of Nrf2 in early eukaryotes and used virtual screens to predict natural products able to activate Nrf2 by competitive inhibition of Keap1-Nrf2 binding. Mycosporine-like amino acids (MAAs) are water-soluble metabolites produced by taxonomically diverse organisms, particularly marine algae and seaweeds. These compounds absorb UV radiation – thus acting as “primary sunscreens” – and reported also to protect against oxidative damage. We have tested the MAAs, porphyra-334, shinorine, and palythine for in-vitro antioxidant activity using the DPPH free-radical quenching assay and report also their ability to activate the Keap1-Nrf2 pathway using fluorescence polarization and thermal shift assays to detect Keap1 receptor antagonism. Our results demonstrate that shinorine and porphyra-334 are competitive inhibitors of Keap1-Nrf2 binding having potential to protect against UVR via sunscreen absorption and transcriptional activation of endogenous defenses against UV-induced oxidative damage.

KW - Antioxidant

KW - Nrf2

KW - Natural Products

KW - Oxidative stress

KW - Mycosporine-like amino acid

U2 - 10.1016/j.freeradbiomed.2017.04.096

DO - 10.1016/j.freeradbiomed.2017.04.096

M3 - Meeting abstract

SN - 0891-5849

VL - 108, Supplement 1

SP - S21

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -