ARS Heath Family Grant

The successful applicant for the ARS Project Grant was:

Principal Applicant
Professor Helen Galley
University of Aberdeen

Title
Does pyrroloquinoline quinone (PQQ) have potential as a novel therapy to prevent oxidative stress and mitochondrial dysfunction under conditions of sepsis?

Amount
£12,407

Scientific Abstract
Main research question
Pyrroloquinoline quinone (PQQ) and melatonin are antioxidants and both can influence mitochondrial biogenesis and mitochondrial antioxidant capacity by activating the transcription coactivator peroxisome proliferator-activated receptor- -coactivator-1 PGC1. PQQ is thought to be better than melatonin in stimulating PGC1 pathways during oxidative stress, but it is unknown if PQQ represents a more effective alternative to melatonin under conditions of sepsis.

Plan of investigation
In this study human cells will be exposed to an inflammatory insult. We will examine the effect of PQQ compared to melatonin on immune modulation, mitochondrial function, and determine the signalling pathways involved in mitochondrial biogenesis, metabolism and antioxidant protection under conditions of sepsis.

Methodology
Two methodological approaches will be used to test the efficacy of PQQ: directly stimulating whole blood with bacterial cell wall components to mimic sepsis, or exposing endothelial cells and isolated white blood cells to plasma containing the secreted factors arising from the immune cell activation. Mitochondrial function will be quantified using various methods and related to antioxidant capacity and downstream signalling involved in enhanced mitochondrial function.

Main outcome measures
The main outcome of this study whether PQQ is shown to be a promising drug to take forward into subsequent translational studies.

 Final report from Prof H Galley (256 KB)