June 13, 2013

New Liver Disease Test Provided By Glowing Proteins From Eels

A new fluorescent protein from unagi eels, commonly found in sushi, is the basis for a revolutionary liver disease test.

By Nsikan Akpan, PhD | Jun 13, 2013 12:01 PM EDT

A newly discovered protein in eels glows when it comes in contact with bilirubin, a natural byproduct of liver damage, according to Japanese scientists from RIKEN Brain Science Institute. In their study, researchers adapted this fluorescent protein, the first found in vertebrate species, into a quick, ultra sensitive test for liver damage that could ultimately save lives.

If you've ever been to a fancy sushi restaurant, then you might already be familiar with unagi, the Japanese freshwater eel (Anguilla japonica). Unagi is Japanese delicacy, which spends most of its life swimming in the streams and rivers of Japan, but during adulthood, will venture thousand of miles into the Philippine Sea to breed.

While studying the eel in 2009, a separate research group found its muscle fibers glow yellow when a bluish-green light is shined on them.

Drs. Akiko Kumagai and Atsushi Miyawaki led a team of scientists who were able to extract the 'light-emitting' protein from the eel's muscles. But the luminescence from the protein, which they named UnaG, was very faint on its own.

Given that the eel's muscle tissue emitted a stronger glow, the researchers suspected 'a partner in shine.' In other words, UnaG might interact with another compound that helps it to glow.

They mixed UnaG protein with a variety of biological substances, and their test tubes lit up when the eel protein was combined with serum from cow or human blood. A series of tests revealed the co-partner was a yellow compound called bilirubin.

Bilirubin is a waste product generated by the breakdown of blood cells. The liver is in charge of packing bilirubin, so it can be excreted by urination or as bile in the gallbladder.

One of the first signs of liver disease, such a hepatitis or liver cancer, is jaundice or a yellowing of the skin and eyes. Jaundice is caused by an accumulation of too much biliruibin in the blood.

The authors found that UnaG protein could be used as quick, sensitive method for measuring small quantities of bilirubin in human blood. They propose that it can improve upon the current bilirubin test, which has been around since 1916.

The gene that makes the UnaG protein has been cloned and inserted into laboratory bacteria strains, so eels would not need to be sacrificed to mass produce a new bilirubin test.

UnaG protein could be processed and stored at room temperature, which would make it easy to ship to remote rural areas in Indonesia or Africa, where hepatitis is endemic.

This discovery could also mean great things for the unagi eel. Overfishing and possibly global warming have decimated its population, and the eel was added to the endangered species list in February.

The authors proposed that much more could be learned from unagi eels, as a separate experiment suggested that the UnaG protein may help the eels fight muscle fatigue during their long journeys to sea. They also found similar proteins in other species of eels.

These findings may lead to the eel becoming a protected species.

"We believe that UnaG provides an unexpected foothold into several important but currently obscure areas of human health including bilirubin metabolism and muscle physiology during endurance exercise," Miyawaki concluded. "Before the discovery of UnaG, I couldn't imagine that basic science could have such a direct impact on human health. From a simple eel, we found a new path to the clinic."

Source: Kumagai A, Ando R, Miyatake H, et al. A Bilirubin-Inducible Fluorescent Protein from Eel Muscle. Cell. 2013.

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