Navigation Links
How do infections and toxins launch a cell's self-destruct and alarm system?
Date:3/10/2008

Cells are coded with several programs for self-destruction. Many cells die peacefully. Others cause a ruckus on their way out.

Some programmed cell death pathways simply and quietly remove unwanted cells, noted a team of University of Washington (UW) researchers who study the mechanisms of cell destruction.

Then there is the alarm-ringing death of a potentially dangerous cell, such as a cell infected with Salmonella, they added. These dying cells spill chemical signals and get a protective response. The resulting inflammation, which the body launches in self-defense, can at times backfire and damage vital tissues.

A research team lead by Dr. Brad T. Cookson, an associate professor of microbiology and laboratory medicine, named this type of cell death "pyroptosis," Greek for going down in flames. Cell death that doesn't cause inflammation is called "apoptosis": to drop gently like leaves from a tree.

An enzyme inside cells, called caspase-1, plays a critical role in both harmful inflammation and in resistance to infection, Cookson and his colleagues noted. It's not just responsible for cell death, but also for the production of inflammatory proteins that are released from the dying cell. Mice deficient in caspase-1 are susceptible to infection, yet resistant to toxic shock, tissue injury from lack of oxygen, and inflammatory bowel disease.

The Cookson lab has done many studies of caspase-1 and how it mediates the pathway of pro-inflammatory programmed cell death. The lab's most recent study will be published the week of March 10 to March 14 in the online Early Edition of the Proceedings of the National Academy of Sciences. The study looked at how two different noxious stimuli, anthrax toxin and Salmonella infection, trigger the caspase-1-mediated cell death pathway. UW graduate students Susan Fink and Tessa Bergsbaken conducted this study.

The researchers found that each of these stimuli took an independent route to activate caspase-1; however, these two distinct mechanisms of activation eventually converged on a common pathway of cell death. This common pathway featured cleavage of the cell's DNA, activation of inflammatory chemical messengers, and the final jettison of the cells contents. The spillage occurs after nano-scale pores form in the cell membrane, much like punctures in a water balloon.

According to Cookson, these findings are helping to create research models for studying a broadly important pathway of pro-inflammatory programmed cell death. The findings also support the notion that diverse disease agents can use different mechanisms to elicit this pathway.

"Examining this system provides insight into mechanisms of both beneficial and pathological cell death, and the strategies that infectious disease agents employ to manipulate the body's responses," Cookson said. His group's previous studies of Yersinia, the plague pathogen, revealed that cell death mechanisms can be re-directed from a passive, non-inflammatory pathway, to a more beneficial inflammatory pathway. This finding suggests the possibility of treating diseases by modulating cell death pathways.

"In addition to its protective role in fighting infection," Cookson added, "caspase-1 also plays a role in many medical conditions characterized by cell death and inflammation." These conditions include organ damage in the heart, brain, lungs, nerves, and kidneys. Understanding pro-inflammatory cell death pathways may lead to new therapies against fatal or disabling diseases, such as serious infections, heart attack, cancer and stroke.

Cookson is part of the National Institutes of Health-funded Microscale Life Sciences Center, a collaboration among scientists and engineers from the UW, the University of Arizona, the Fred Hutchinson Cancer Research Center, and Brandeis University. The scientists work to discover basic mechanisms in the formation, growth, and decline of human cells. Their aim is to develop biotechnology to combat widespread diseases and environmental threats to human health.


'/>"/>

Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

Related medicine news :

1. New research from the University of Bristol aims to eliminate Streptococcus infections
2. Hospital Testing for Drug-Resistant Infections Dramatically Lowers Mortality Rates and Costs
3. Researchers find possible target to treat deadly bloodstream infections
4. Gene expression differences between Europeans and Africans affect response to drugs, infections
5. APIC Selected as Faculty in Blue Shield of California Foundation Initiative to Fight Healthcare-Associated Infections
6. Viral Infections Tied to Pregnancy Complications
7. Public Health Experts Argue for Integrated Services to Avert 7 Million HIV Infections by 2010
8. Microsoft Introduces Patient Safety Screening Tool to Stop Spread of In-Hospital Infections
9. UCF technique promises to aid doctors ability to identify, treat bacterial infections
10. Antibiotics Do Little for Inner Ear Infections
11. Novel mathematical model predicts new wave of drug-resistant HIV infections in San Francisco
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
How do infections and toxins launch a cell's self-destruct and alarm system?
(Date:6/26/2016)... ... June 26, 2016 , ... ... they have been diagnosed with endometriosis. These women need a treatment plan to ... a comprehensive approach that can help for preservation of fertility and ultimately achieving ...
(Date:6/25/2016)... , ... June 25, 2016 , ... First Choice ... States, named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell Farm ... Medical Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive Medical ...
(Date:6/24/2016)... ... 24, 2016 , ... A recent article published June 14 on ... article goes on to state that individuals are now more comfortable seeking to undergo ... such as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills ...
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg ... Legal Elite. The attorneys chosen by their peers for this recognition are considered among ... Greenberg Traurig Shareholders received special honors as members of this year’s Legal Elite Hall ...
(Date:6/24/2016)... ... 2016 , ... EB Medicine presented its first-ever “Issue of ... in Ponte Vedra Beach, FL. The awards honor the outstanding work of leading ... and Pediatric Emergency Medicine Practice. , “With this award, we recognize the efforts ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016  Arkis BioSciences, a leading ... and more durable cerebrospinal fluid treatments, today announced ... Series-A funding is led by Innova Memphis, followed ... other private investors.  Arkis, new financing will accelerate ... the market release of its in-licensed Endexo® technology. ...
(Date:6/23/2016)... 23, 2016 Research and Markets has ... - Forecast to 2022" report to their offering. ... for the patients with kidney failure, it replaces the function ... the patient,s blood and thus the treatment helps to keep ... in balance. Increasing number of ESRD patients ...
(Date:6/23/2016)... DUBLIN , June 23, 2016 ... the "Pharmaceutical Excipients Market by Type (Organic Chemical ... Preservative), Formulation (Oral, Topical, Coating, Parenteral) - Global Forecast ... The global pharmaceutical excipients ... 2021 at a CAGR of 6.1% in the forecast ...
Breaking Medicine Technology: