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Heloderma suspectum |
Lizards and other reptiles are not normally
considered venomous, but a number of lizard species actually do produce and use
venom. The most classic venomous lizard is no doubt the gila monster -- a
heavy-bodied lizard. As the first in the world, a group of researchers has made
a comprehensive description of the proteins in the venom which can prove to be
relevant in connection with developing new types of drugs.
Gila
and beaded lizards are the classic venomous lizards. However, it was recently
shown that venom is also used by a number of other species, such as the awesome
Komodo monitors -- the largest present-day lizards. Lizard venom has much in
common with snake venom, and the current theory is that the venom production
apparatus in lizards and snakes is related, but has developed in different
directions. Gila and beaded lizards mainly use venom to defend themselves,
while snakes use their venom to attack prey. However, the composition of venom
proteins is similar in lizards and snakes.
Venom
research is a large field, especially due to the pharmaceutical potential of
the venom proteins. The idea here is that venom proteins are capable of
affecting the body's cells. Excessive amounts can be harmful and even lethal in
some circumstances, but if the right dose is used, the venom proteins can be
used to treat certain diseases. Snake proteins that normally cause prey to
bleed can be used in small doses to treat blood clots, for example. In the same
way, work is currently being done to develop spider venom proteins to provide
pain relief. The Aarhus researchers focused on Gila lizards, and these are
currently being used in pharmaceutical contexts. Gila lizards produce
exendin-4, a small venom protein used in the treatment of diabetes and obesity,
which is a competitor to Victoza® -- produced by Novo Nordisk.
A
method called proteomics was used in the Aarhus study to make the first overall
description of venom proteins in Gila lizards. Individual proteins such as exendin-4
used to be purified from Gila lizard venom, and this resulted in a number of
interesting results. However, an overall analysis of all the venom proteins has
not been undertaken before, which therefore made it easy to overlook the
potentially important components in the venom.
Making
a comprehensive analysis of the venom protein composition was not an easy task.
"The work was complicated by the fact that the Gila lizard genome hasn't
been isolated, and genomes normally provide a map to navigate when you're using
proteomics for protein identifications," says Associate Professor Kristian
Wejse Sanggaard. "We therefore used a more manually based approach to
identify the proteins in the Gila lizard venom. This succeeded, and we've
identified nineteen proteins that no one previously knew existed in the
venom," he concludes.
Based
on these identifications, the researchers have gained new knowledge about the
function of the venom proteins, and have also gained greater insight into the
evolutionary contexts of venom proteins. In addition, there are now new
proteins that can potentially be used to develop future drugs.
Citation
Sanggaard
KW, Dyrlund TF, Thomsen LR, Nielsen TA, Brøndum L, Wang T, Thøgersen IB, Enghild
JJ. Characterization of the gila monster (Heloderma suspectum suspectum)
venom proteome. Journal of Proteomics, 2015; 117: 1 DOI: 10.1016/j.jprot.2015.01.004