Featured Research

from universities, journals, and other organizations

Copper's previously unknown exit strategy from the body

Date:
July 13, 2012
Source:
Johns Hopkins Medicine
Summary:
Scientists have long known that the body rids itself of excess copper and various other minerals by collecting them in the liver and excreting them through the liver’s bile. However, a new study suggests that when this route is impaired there’s another exit route just for copper: A molecule sequesters only that mineral and routes it from the body through urine.

Scientists have long known that the body rids itself of excess copper and various other minerals by collecting them in the liver and excreting them through the liver's bile. However, a new study led by Johns Hopkins researchers and published June 22 in PLoS One suggests that when this route is impaired there's another exit route just for copper: A molecule sequesters only that mineral and routes it from the body through urine.

Related Articles


The researchers, led by Svetlana Lutsenko, Ph.D., a professor of physiology at the Johns Hopkins University School of Medicine, found this additional copper escape hatch by studying an animal model of Wilson's disease, a rare disorder most often diagnosed in children. People with this disease accumulate abnormally large amounts of copper in the liver, eventually leading to liver damage and failure.

Micronutrients such as copper, zinc and iron are indispensible for human development. Copper is required for embryonic development, respiration, and cardiovascular function, among other processes; too little copper can be fatal whereas too much can cause neurological impairment and organ failure.

One diagnostic test for Wilson's disease is to check for high amounts of copper in the urine; copper levels could be especially high in advanced stages of this disorder. For decades doctors and scientists have blamed this high urinary copper on the breakdown of cells in the liver, which purportedly dumped their contents into the bloodstream as they died. These contents were thought to be picked up by the kidneys and eventually excreted in the urine.

However, Lutsenko says, this theory had never been tested. To verify this explanation, she and her colleagues examined mice genetically modified to have Wilson's disease. As in people, these animals' liver function gradually worsens over time due to copper accumulation. Eventually the animals' livers regenerate and liver function improves and with this the researchers expected to see less urinary copper. However, at this stage in the disease, urinary copper in the animal models continued to increase. Additionally, the researchers found no increased urine concentrations of other minerals stored in liver cells, which would be expected if these cells were releasing all their entire contents and not just copper. Together, these findings suggest that liver cell death isn't the main source of urinary copper in Wilson's disease.

Delving deeper, the researchers gave the mice radioactive copper, which they could trace as it made its way through the body. They found that when copper reached a certain threshold level in the liver, it was directed it to the kidneys instead. At the same time, they saw that levels of a protein used to transport copper to the liver decreased. Both of these observations strengthened the idea that another mechanism must exist to remove copper from the body.

To figure out what that mechanism might be, Lawrence Gray, a graduate student on Lutsenko's team searched the animals' urine to see what molecules copper might be bound to. Their pursuit turned up an unidentified molecule that they've temporarily named "small copper carrier," or SCC. Further tests showed that as liver function decreased, more SCC appeared in the animals' blood, and that SCC could compete for copper with the proteins that normally transport this mineral to the liver.

"These findings all suggest that SCC indeed represents a previously unknown agent that the body uses to excrete excess copper," Lutsenko explains.

She and her colleagues are now trying to learn more about SCC, both to identify this molecule and to determine whether it could be a unique marker that's only present during Wilson's disease. If so, it could save pediatric patients the pain of liver biopsy, a test often used to definitively diagnose this condition. In addition, SCC may also represent a treatment for this rare disorder. If scientists could develop a way to raise SCC concentration in the blood, Lutsenko says, it could increase copper export and prevent further harm to the liver.

This study was funded by the National Institutes of Health grants 5F31DK084730, 5R01DK079209, and 5P01GM067166. The mass-spectrometry work was done at the Oregon Health and Science University, supported by NIH instrumentation grant S10-RR025512.

Authors on the paper are Lawrence Gray, Venkata S. Pendyala, Abigael Muchenditsi and Svetlana Lutsenko of Johns Hopkins; Fangyu Peng of University of Texas Southwestern Medical Center; Shannon A. Molloy and Jack H. Kaplan of University of Illinois at Chicago; Otto Muzik of Wayne State University, School of Medicine, Detroit, Michigan; and Jaekwon Lee of University of Nebraska, Lincoln.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lawrence W. Gray, Fangyu Peng, Shannon A. Molloy, Venkata S. Pendyala, Abigael Muchenditsi, Otto Muzik, Jaekwon Lee, Jack H. Kaplan, Svetlana Lutsenko. Urinary Copper Elevation in a Mouse Model of Wilson's Disease Is a Regulated Process to Specifically Decrease the Hepatic Copper Load. PLoS ONE, 2012; 7 (6): e38327 DOI: 10.1371/journal.pone.0038327

Cite This Page:

Johns Hopkins Medicine. "Copper's previously unknown exit strategy from the body." ScienceDaily. ScienceDaily, 13 July 2012. <www.sciencedaily.com/releases/2012/07/120713091607.htm>.
Johns Hopkins Medicine. (2012, July 13). Copper's previously unknown exit strategy from the body. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2012/07/120713091607.htm
Johns Hopkins Medicine. "Copper's previously unknown exit strategy from the body." ScienceDaily. www.sciencedaily.com/releases/2012/07/120713091607.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins