Featured Research

from universities, journals, and other organizations

Scientists identify key protein linked to acute liver failure: Inhibition of protein protects liver from acetaminophen toxicity in mice

Date:
September 7, 2011
Source:
University of Southern California
Summary:
New research shows that inhibition of the Sab protein prevents liver damage associated with acetaminophen overdose. The results suggest that inhibition of the protein can protect against various types of cellular death in any organ.

New research from the Keck School of Medicine of the University of Southern California (USC) may help prevent damage to the liver caused by drugs like acetaminophen and other stressors.

Acetaminophen, more commonly known as Tylenol, helps relieve pain and reduce fever. The over-the-counter drug is a major ingredient in many cold and flu remedies as well as prescription painkillers like Percocet and Vicodin.

However, metabolized by the liver, acetaminophen is the most common cause of drug-induced liver disease and acute liver failure in the United States and United Kingdom. Tylenol's maker announced in July that it was lowering the maximum recommended daily dosage to 3,000 milligrams to help prevent accidental overdoses.

Doctors at the Keck School of Medicine of USC have identified a protein on the mitochondria of liver cells in mice that, when silenced, protects against liver toxicity usually associated with excess doses of acetaminophen.

They found that the protein Sab, or SH3-domain binding protein 5, binds with the enzyme JNK (c-Jun N-terminal kinase). JNK regulates cellular metabolism and survival in response to stress, protecting cells when activated for brief intervals. However, JNK also kills cells when activated for prolonged periods of time.

"Because the short-term activation of JNK is associated with cell survival, Sab is potentially a better target than inhibiting JNK, which could have adverse effects," said Neil Kaplowitz, M.D., the study's lead investigator and professor of medicine at the Keck School.

Researchers have long believed that acetaminophen was converted into toxic metabolites that, in excess, overwhelm liver cells, causing them to die. In a 2008 study, Kaplowitz, who holds the Keck School's Thomas H. Brem Chair in Medicine and Veronica P. Budnick Chair in Liver Disease, and other USC colleagues turned that theory around -- they found that it was not the metabolite, but rather the sustained activation of JNK that harmed the organ. By inhibiting JNK activation in mice, injury to the liver caused by large doses of acetaminophen was avoided.

In the current study, published online by the Journal of Biological Chemistry in August, the scientists silenced Sab in mice, which did not affect the metabolism of acetaminophen but successfully prevented liver injury. They also tested the effect on liver injury caused by apoptosis, or programmed cell death in response to inflammatory proteins that are implicated in many diseases and tissues -- silencing Sab protected the liver in that case, too.

"We proved that the sustained activation of JNK targets Sab and is a requirement for the subsequent death of liver cells," Kaplowitz said. "We then showed that it is a universal effect. Developing a drug to protect against cell death, one could argue to target JNK -- but that's a double-edged sword. This provides a whole new target: Create a drug that inhibits the interaction between JNK and Sab."

Co-authors include Sanda Win, Tin Aung Than, Derick Han and Lydia M. Petrovic. Their research was funded by the National Institutes of Health.


Story Source:

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


Journal Reference:

  1. S. Win, T. A. Than, D. Han, L. M. Petrovic, N. Kaplowitz. JNK dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial SAB expression in mice. Journal of Biological Chemistry, 2011; DOI: 10.1074/jbc.M111.276089

Cite This Page:

University of Southern California. "Scientists identify key protein linked to acute liver failure: Inhibition of protein protects liver from acetaminophen toxicity in mice." ScienceDaily. ScienceDaily, 7 September 2011. <www.sciencedaily.com/releases/2011/09/110907163904.htm>.
University of Southern California. (2011, September 7). Scientists identify key protein linked to acute liver failure: Inhibition of protein protects liver from acetaminophen toxicity in mice. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2011/09/110907163904.htm
University of Southern California. "Scientists identify key protein linked to acute liver failure: Inhibition of protein protects liver from acetaminophen toxicity in mice." ScienceDaily. www.sciencedaily.com/releases/2011/09/110907163904.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Nigeria Ups Ebola Stakes on 1st Death

Nigeria Ups Ebola Stakes on 1st Death

Reuters - Business Video Online (July 29, 2014) Nigerian authorities have shut and quarantined a Lagos hospital where a Liberian man died of the Ebola virus, the first recorded case of the highly-infectious disease in Africa's most populous economy. David Pollard reports Video provided by Reuters
Powered by NewsLook.com
Running 5 Minutes A Day Might Add Years To Your Life

Running 5 Minutes A Day Might Add Years To Your Life

Newsy (July 29, 2014) According to a new study, just five minutes of running or jogging a day could add years to your life. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Poses Little Threat To U.S.: CDC

Ebola Outbreak Poses Little Threat To U.S.: CDC

Newsy (July 29, 2014) The Ebola outbreak in West Africa poses little threat to Americans, according to officials with the Centers for Disease Control and Prevention. 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:
from the past week

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