Research by the University of Warwick, the University Hospital Coventry and Warwickshire NHS Trust (UHCW), and Tangent Reprofiling Limited, has discovered that statin drugs interact with a gap junction protein called GJC3 that releases ATP, a major signaling molecule for inflammation in the body. This discovery provides a significant new target in the search for why statin drugs can sometimes cause harmful effects such as muscle toxicity in some patients.
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| GJC3 gap junction proteins |
Speaking on behalf of the team in
the Department of Chemistry at the University of Warwick, Dr Andrew Marsh
said:
“Statins are
powerful cholesterol-lowering medicines that are widely prescribed to reduce
the burden of cardiovascular disease. Gap junction proteins are important in
forming communication channels between cells and organs in the body. In this
new research, two clinically used statin therapeutics have been found to
interact with an important part of GJC3, a gap junction protein which acts to
release ATP, a signaling molecule that is key to the body’s response to injury
and inflammation.
“Many people know ATP as the
cell’s main energy transfer molecule, but when released outside cells, ATP
coordinates how tissues including our liver and muscles deal with recovery from
injury. These results may give us better understanding of how some of the
harmful effects of statins in some patients, such as muscle toxicity, might
come about”.
The new research paper entitled “Simvastatin
sodium salt and fluvastatin interact with human gap junction gamma-3 protein” http://dx.plos.org/10.1371/journal.pone.pone.0148266
is published on Wednesday 10th
February 2016 in the open access journal PLOS ONE. The
study was a collaboration between scientists and clinicians at the University
of Warwick, the University Hospital Coventry and Warwickshire NHS Trust (UHCW) and
Tangent Reprofiling Limited.
The researchers found that the statins
simvastatin sodium salt and fluvastatin were found to interact with a peptide
from the gap junction protein GJC3. In work which confirmed the observed
interaction, the researchers also found that certain pharmacological probes of
other gap junction proteins are also bound to the peptide sequence they had identified. The orange colour in the Figure highlights the important portions of GJC3 gap junction
proteins.
University of Warwick research
chemist Dr Andrew Marsh also said that
“GJC3 is present in many tissues
in the body, but its role in cell signaling is poorly understood. Our work
opens doors to its investigation”.
Professor Donald Singer, President
of the Fellowship of Postgraduate Medicine and who was the lead investigator of
the teams working on this study in Warwick Medical School and UHCW commented
“Finding additional ways in which
statins act at the cellular and molecular level is important for giving clues
to potential new medical applications for these drugs.
"These results may also
give us better understanding of how some of the harmful effects of statins in
some patients might come about”.
Notes for editors:
The research refers to the open access journal PLOS ONE paper http://dx.plos.org/10.1371/journal.pone.pone.0148266, 10 Feb 2016 and the paper was entitled Simvastatin
sodium salt and fluvastatin interact with human gap junction gamma-3 protein”. PLOS ONE publishes work from science
and medicine and “facilitates the discovery of connections between research
whether within or between disciplines”.
The work was funded by the
Engineering and Physical Sciences Research Council (EPSRC, UK), the University
of Warwick and Tangent Reprofiling Limited. EPSRC’s vision is “for the UK to be
the most dynamic and stimulating environment in which to engage in research and
innovation.”
Equipment used in this research
was obtained through Birmingham Science City: Innovative Uses for Advanced
Materials in the Modern World with support from Advantage West Midlands (AWM)
and part funded by the European Regional Development Fund (ERDF).
For further information please contact:
Dr Andrew
Marsh,
Department of Chemistry,
University of Warwick, Coventry CV4 7AL. Tel. +44 24 7652 4565
or
Peter Dunn, Director of Press and Policy,
University of Warwick, Tel UK: 024 76523708
office 07767 655860 mobile
Tel
Overseas: +44 (0)24 76523708 office +44 (0)7767 655860 mobile/cell
Email: p.j.dunn@warwick.ac.uk
PR31 PJD 9th February
2016
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