Featured Research

from universities, journals, and other organizations

Toxic Compound Opens Potentially Important Cell Gates

Date:
June 27, 2001
Source:
Johns Hopkins University
Summary:
A compound previously noted mainly for its role in disease and the self-destruction of sick cells is more than just a jobless, toxic transient in healthy cells, researchers have found.

A compound previously noted mainly for its role in disease and the self-destruction of sick cells is more than just a jobless, toxic transient in healthy cells, researchers have found.

Related Articles


Scientists from The Johns Hopkins University, Harvard University and The University of Hawaii have reported new evidence rehabilitating the reputation of this biological pariah, known as adenosine diphosphate ribose, or ADP-ribose. They found that as cells work to break the compound down, a pause in the disposal process allows ADP-ribose to open a gate for transporting calcium through cell membranes in the brain, lungs, heart, spleen, liver, kidney, and elsewhere.

"It's important to know what opens and closes calcium channels, because calcium transport into and out of cells is a significant step in a wide variety of physiological processes," says Maurice Bessman, professor of biology in the Krieger School of Arts and Sciences at Hopkins and an author of a paper in the May 31 issue of "Nature." "Examples include nerve cell signaling processes, regulation of the heartbeat and muscle contraction, immune system responses, olfaction, and energy metabolism."

Researchers found evidence that a protein originally used solely to break down ADP-ribose had become fused with a protein that creates a calcium channel known as LTRPC2. A key segment of the disposal protein apparently was incorporated through evolution into the larger protein that creates the calcium channel.

"Two different processes -- two old functions -- have been very tightly tied together, but they're both still carrying out their own individual enzymatic reactions," Bessman says. "You get a whole that is greater than the sum of its parts. We don't think this is the last example of this type of fusion, and will be looking for other similar proteins usurped for other functions in a comparable fashion."

Discovery of the link began when Andrew Scharenberg's lab at Harvard Medical School, which specializes in calcium channels' roles in the immune system, identified two genes that they thought were linked to calcium channels.

Scharenberg noted that both genes contained a section of DNA similar to a DNA segment that is the defining characteristic of a family of genes Bessman's group discovered and calls "Nudix" hydrolases. The characteristic section of these genes is known as a "Nudix box."

"We think this family of genes has been around for a long time," says Christopher Dunn, a research technician at Hopkins and an author on the "Nature" paper. "Although the proteins we worked with in this particular project are from humans, the Nudix hydrolases are found in the most primitive to the highest organisms, with nearly 600 members in 200 species identified so far."

Cells most commonly use Nudix proteins as "housecleaners"that break apart potentially harmful derivatives of nucleoside diphosphates, but Bessman's group has also shown Nudix proteins have been adapted to a variety of other functions.

Scharenberg sent clones of the Nudix genes he'd found to Bessman, and Dunn transferred the shorter gene into E. coli bacteria. When the bacteria used the gene to make proteins, Dunn tested them against a series of compounds that bind to Nudix boxes. The protein would only bind to ADP-ribose, a toxic biochemical that is used by some organisms including diptheria to disable cells.

"ADP-ribose is also involved in apoptosis, a self-destruct mechanism used by sick or genetically damaged cells," says Dunn. "Free ADP-ribose is released all the time in healthy cells as a byproduct of other reactions, but it's always cleaned up."

The second, larger gene identified by Scharenberg had a Nudix box at one end. When Bessman and Dunn isolated that segment of the larger protein and repeated the experiment they'd performed on the shorter gene, they found that it also would only bind to ADP-ribose.

Suspecting that the remainder of the second protein was involved in the formation of a calcium ion channel, Scharenberg and Bessman asked Reinhold Penner of the University of Hawaii at Honolulu to use a special "patch-clamp" technique to test whether LTRPC2 created a channel and whether that channel could be regulated with ADP-ribose. He found that the answer to both questions was yes.

"In fact, Reinhold found that the mechanism was very specific; other compounds can't open the channel," Bessman says. "This effort, in which three labs with different expertises worked toward a common goal, was a paradigm of scientific cooperation," Bessman concludes. "It's a bit like the fusion of the proteins we found; the whole was greater than the sum of its parts."

Other authors on the paper were Anne-Laure Perraud, Pierre Launay, Carsten Schmitz, Alexander Stokes, Qiqin Zhu, and Jean-Pierre Kinet, of Harvard; and Andrea Fleig and Leigh Ann Bagley of the University of Hawaii.

This research was supported by the National Institutes of Health and by a grant from the Beth Israel Pathology Foundation.


Story Source:

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


Cite This Page:

Johns Hopkins University. "Toxic Compound Opens Potentially Important Cell Gates." ScienceDaily. ScienceDaily, 27 June 2001. <www.sciencedaily.com/releases/2001/06/010611071100.htm>.
Johns Hopkins University. (2001, June 27). Toxic Compound Opens Potentially Important Cell Gates. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2001/06/010611071100.htm
Johns Hopkins University. "Toxic Compound Opens Potentially Important Cell Gates." ScienceDaily. www.sciencedaily.com/releases/2001/06/010611071100.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
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