Warning mechanism and cell self-destruction when poisoning or disease

Cells are encoded with a number of programs to self-destruct. Many cells die peacefully while others do it hard. According to notes by a group of Washington University scientists studying the mechanism of cell destruction. Some cell deaths are simply removing silently unnecessary cells.

However, they added that there is a kind of death that alarms dangerous cells, such as those infected with Salmonella. These cells, when dying, emit chemical signals and receive a protective response. That causes inflammation, which causes the body to initiate self-defense mechanisms, which sometimes go too far and destroy important cells.

The team was led by Dr. Brad T. Cookson, a professor of microbiology and laboratory medicine, named the dead cell " pyroptosis ", the Greek word for ' burning in fire '. Cell death does not cause swelling, inflammation called " apoptosis ": leave gently as leaves fall.

An enzyme inside the cell, called caspase-1, plays an important role in both harmful inflammation and in fighting infection. It is not only responsible for cell death, but also for the production of inflammatory proteins produced by dead cells. Mice lacking caspase-1 are susceptible to infection but are resistant to toxic shock, tissue damage due to hypoxia and inflammatory bowel disease.

The Cookson laboratory has done a lot of research on caspase-1 and how to regulate the cell death due to swelling. The most recent study was published in the week from March 10 to March 14 on the online edition of Proceedings of the National Academy of Sciences . The study investigated two different types of toxic stimuli, anthrax and Salmonella, and caspase-1-controlled cell death . Two graduate students of Washington University Susan Fink and Tessa Bergsbaken conducted this work.

Diagram illustrating the mechanism of cell death pyroptosis.When activated with a toxin or a disease, the caspase-1 enzyme initiates some reactions inside the cell, some of which lead to DNA destruction, others release the chemical signal degradation of cytokines and also membrane-forming reactions of small holes for water to enter.The cells will become swollen, ruptured and overflow with internal substances.(Photo by David W. Ehlert and Brad Cookson, University of Washington)

The researchers found that each of these stimuli has a different way of activating caspase-1. However, the two separation mechanisms eventually lead to a similar way of cell death. That way involves separating the cell's DNA, activating inflammatory signaling chemicals, and final cell elongation. This occurs when nano-sized holes form in the cell membrane, similar to small spots in a water bubble.

According to Cookson, the finding will help to create patterns to study important ways of swollen cell death. These findings support the concept: many different diseases can use different mechanisms to activate this path.

Cookson said: 'System testing can provide knowledge of the mechanism that causes cell death, either beneficial or pathological, and the strategy of dangerous infectious diseases used to manipulate the reaction of body. The group's previous work on Yersinia, the source of the epidemic, revealed that the mechanism of cell death could be controlled from passive, non-inflammatory to a more beneficial way. The work shows the healing ability by controlling cell death. "

In addition to having a protective role in fighting disease, caspase-1 also plays an important role in many medical conditions characterized by cell death and inflammation. These conditions include organ damage such as heart, kidney, brain, lungs, nerves and kidneys. Understanding the mechanism of inflammatory cell death can lead to therapy for deadly diseases like heart attack, cancer, stroke and serious infections.

Cookson is a member of the Micro Life Sciences Center sponsored by the National Institutes of Health Research, an alliance between scientists and engineers at the University of Washington, University of Arizona, Fred Cancer Research Center. Hutchinson and Brandeis University. Scientists collaborate to discover the basic mechanism in the formation, development and impairment of human cells. Their goal is to develop biotechnology against infectious diseases and environmental hazards to human health.