Featured Research

from universities, journals, and other organizations

Jekyll and Hyde: Cells' executioner can also stave off death

Date:
March 5, 2011
Source:
Emory University
Summary:
An enzyme viewed as an executioner, because it can push cells to commit suicide, may actually short circuit a second form of cell death, researchers have discovered. The finding could shift drug discovery efforts, by leading scientists to rethink how proposed anti-cancer and anti-inflammatory drugs that target the enzyme, called caspase 8, are supposed to work.

An enzyme viewed as an executioner, because it can push cells to commit suicide, may actually short circuit a second form of cell death, researchers at Emory University School of Medicine have discovered.

The finding could shift drug discovery efforts, by leading scientists to rethink how proposed anti-cancer and anti-inflammatory drugs that target the enzyme, called caspase 8, are supposed to work. The results are online this week and will be published in the March 17th edition of Nature.

Caspase 8 has been described as "the killer you can't live without." This enzyme plays a key role in apoptosis, a form of cellular suicide important for the development of all multicellular organisms, and in defense against viral infections. Mice lacking caspase 8 die before birth, because their blood vessels and blood-forming stem cells fail to develop properly. In the Nature paper, Emory researchers show that mice without caspase 8 develop normally if they also lack another enzyme called RIP3.

"The surprising aspect is that caspase 8 appears to have two functions: one that initiates apoptosis and a second that restrains an independent programmed death pathway," says senior author Ed Mocarski, PhD, Robert W. Woodruff Professor of Microbiology and Immunology at Emory Vaccine Center and Emory University School of Medicine.

Graduate student William Kaiser, in Emory's Microbiology and Molecular Genetics program, is the first author of the paper. Other Emory authors include Tamara Caspary, PhD, assistant professor of human genetics, as well as students and postdoctoral fellows from both Emory labs.

"It's remarkable to be able to rescue mice from embryonic death," Caspary says. "I was surprised that the mice are even born, since these enzymes are basic parts of the cellular machinery."

In humans, a lack of caspase 8 has been linked to immune disorders and skin diseases such as eczema, while too much caspase 8 activity has been connected with diabetes. In addition, several experimental anti-cancer and anti-inflammatory drugs aim to alter caspase 8 levels in order to induce death in cancer cells or reduce inflammation.

"Until recently, scientists viewed programmed cell death mainly as apoptosis, a program of self-destruction deliberately set in motion through signals cells receive from outside," Mocarski says.

For example, apoptosis ensures that white blood cells responding to an infection don't multiply indefinitely. White blood cells have built-on triggers on their surfaces that activate caspase 8, which unleashes a cascade of enzymes that break down the contents of the cell.

In contrast to apoptosis, necrosis was seen as unregulated death by neglect, until the discovery of an alternative form of cell death, driven by RIP3, called programmed necrosis. This looks like necrosis under the microscope, but like apoptosis is orchestrated by the cell from within rather than occurring because of injury or infection. Mocarski's group recently showed that RIP3 enables cells to sabotage themselves if they are infected by a virus, an activity where apoptosis was once thought to be the most important.

"For several years, the puzzle was: what are the non-apoptotic functions of caspase 8, since there are numerous systems that are impacted by not having it," Mocarski says. "Now we have to consider that the absence of caspase 8 is actually revealing death by RIP3."

Mice lacking both caspase 8 and RIP3 have blood vessels and blood cells that look healthy. However, a few months after birth, they develop swollen lymph nodes, because their white blood cells do not go through apoptosis normally. Other scientists have shown that mice that have caspase 8 missing only in the skin have chronic skin inflammation, a condition resembling eczema in humans.

"Our results indicate that whatever caspase 8 was doing in the skin, removing RIP3 takes care of it," Mocarski says.

The National Institutes of Health supported this research.


Story Source:

The above story is based on materials provided by Emory University. The original article was written by Quinn Eastman. Note: Materials may be edited for content and length.


Journal Reference:

  1. William J. Kaiser, Jason W. Upton, Alyssa B. Long, Devon Livingston-Rosanoff, Lisa P. Daley-Bauer, Razqallah Hakem, Tamara Caspary, Edward S. Mocarski. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature, 2011; DOI: 10.1038/nature09857

Cite This Page:

Emory University. "Jekyll and Hyde: Cells' executioner can also stave off death." ScienceDaily. ScienceDaily, 5 March 2011. <www.sciencedaily.com/releases/2011/03/110303111808.htm>.
Emory University. (2011, March 5). Jekyll and Hyde: Cells' executioner can also stave off death. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2011/03/110303111808.htm
Emory University. "Jekyll and Hyde: Cells' executioner can also stave off death." ScienceDaily. www.sciencedaily.com/releases/2011/03/110303111808.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
Powered by NewsLook.com
Attacking Superbugs

Attacking Superbugs

Ivanhoe (Oct. 1, 2014) Two weapons hospitals can use to attack superbugs. Scientists in Ireland created a new gel resistant to superbugs, and a robot that can disinfect a room in minutes. Video provided by Ivanhoe
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