Navigation Links
St. Jude researchers find key step in programmed cell death
Date:2/29/2008

Investigators at St. Jude Childrens Research Hospital have discovered a dance of proteins that protects certain cells from undergoing apoptosis, also known as programmed cell death. Understanding the fine points of apoptosis is important to researchers seeking ways to control this process.

In a series of experiments, St. Jude researchers found that if any one of three molecules is missing, certain cells lose the ability to protect themselves from apoptosis. A report on this work appears in the advance online publication of Nature.

This is probably the first description of what is happening mechanistically that contributes to the ability of cells to delay apoptosis, said James Ihle, Ph.D., the papers senior author and chair of the St. Jude Department of Biochemistry. It provides incredible insights into how three proteins work and how they can control apoptosis.

The molecular interactions that St. Jude researchers describe in Nature play out in nerve cells and blood cells that develop from hematopoietic (blood-forming) stem cells.

A research team elsewhere recently reported that Kostmanns syndrome, a potentially fatal inherited deficiency of granulocytes in children, caused by excessive apoptosis of granulocytes, results from a deficiency in one of the three proteins, called Hax1.

This suggests that the protein is playing basically the same role in humans as we described in mice, Ihle said.

Apoptosis rids the body of faulty or unneeded cells. However, molecular malfunctions that trigger apoptosis may cause some diseases, including Parkinsons disease. Understanding the biochemical interactions that control the extent of programmed cell death could lead to new treatments.

St. Jude biochemists have long studied how cytokinessmall proteins used by neurons and blood-borne cells to communicate messagescontribute to keeping cells alive. For example, they demonstrated earlier that most cytokines controlling hematopoietic cells require an enzyme called Jak2, or Jak3 in lymphocytes, at the receptors where cytokines attached to the cell.

In screening for components that are regulated by the Jak enzymes, the St. Jude team found the Hax1 protein.

That was intriguing because several studies suggested that Hax1 was controlled by cytokine signaling, Ihle said. Also, studies have suggested that if you overexpressed Hax1 in cells, the cells were protected from undergoing apoptosis.

To pursue this lead, the researchers genetically engineered mice that lacked the gene for Hax1. The results showed that apoptosis in the animals brain caused extensive nerve cell degeneration that killed the mice within 10 to 12 weeks. Second, apoptosis in immune-system lymphocytes occurred in the altered mice eight hours sooner than in those with the Hax1 gene, when limited amounts of cytokines were available.

That additional window of survival is extremely important because in the body, cytokines are limiting. Ihle said. The key observation was that Hax1 was important in helping cells to survive. Importantly, what happened to the mice we generated was remarkably similar to what happens if you remove the mitochondrial enzymes called HtrA2 or Parl.

Exploring the similarities, the investigators found that Hax1 and Parl pair up in the inner membrane of the mitochondriatiny chemical packets that serve as the main energy source for cells. HtrA2 is made in the cells cytoplasm and is transported into the mitochondria, where the enzyme must have a region removed for it to be active. This requires snipping away 133 amino acids, the building blocks of proteins. The St. Jude researchers demonstrated that it is the Hax1/Parl pair that positions HtrA2 to allow the precise snipping that is required. Without Hax1, the snipping does not occur and HtrA2 remains inert.

In lymphocytes, members of the Bcl-2 family of proteins both protect and initiate apoptosis. For this reason, Ihle and the researchers explored this family of proteins to understand why lymphocytes needed an active HtrA2 mitochondrial enzyme. This led them to discover that if active HtrA2 were present, the incorporation of a protein called Bax into the mitochondrial outer membrane did not occur. This was significant since accumulation of Bax in the outer mitochondrial membrane allows the release of proteins that set off a chain of biochemical reactions, including the activation of enzymes that are responsible for cell death.


'/>"/>

Contact: Carrie Strehlau
media@stjude.org
901-495-2295
St. Jude Children's Research Hospital
Source:Eurekalert

Related medicine news :

1. Mayo Researchers Look for Explanation Behind High Incidence of Diabetes Among Asian Indians
2. Mayo researchers look for explanation behind high incidence of diabetes among Asian Indians
3. UT Southwestern researchers investigate predictors for sickle-cell-anemia complications
4. Researchers find possible target to treat deadly bloodstream infections
5. Rutgers researchers unlock mysteries of vitamin A metabolism during embryonic development
6. U of Minn researchers discover genetic cancer link between humans and dogs
7. New genetic association with schizophrenia found by researchers
8. Thomson Scientific To Honor Australias Top Researchers With Dedicated Australian Research Day
9. This is your brain on jazz: researchers use MRI to study spontaneity, creativity
10. First look: Princeton researchers peek into deepest recesses of human brain
11. U of Minn researchers find primary alcohol prevention programs are needed for tweens
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/12/2016)... , ... February 12, 2016 , ... Each year, the ... be held in Anaheim, CA at the Anaheim Convention Center. Almost 10,000 physical therapists ... new therapy products in action, learn more about their chosen field and network with ...
(Date:2/12/2016)... ... February 12, 2016 , ... T.E.N., a technology and information ... ISE Southeast Awards 2016. Finalists and winners of the ISE® Awards for both ... and Awards Gala on March 15, 2016 at the Westin Peachtree Plaza, Atlanta. ...
(Date:2/12/2016)... ... February 12, 2016 , ... Every winter, someone is killed, injured or ... West Penn Burn Center, part of the Allegheny Health Network, has partnered with ... the “Space Heaters Need Space” campaign. , “Space Heaters Need Space” aims ...
(Date:2/12/2016)... ... February 12, 2016 , ... The Jones Agency, a family owned ... Texas, is launching a cooperative charity drive with the Tarrant Area Food Bank in ... 50,000 individuals and families in need, the Tarrant County Food Bank offers hope and ...
(Date:2/12/2016)... (PRWEB) , ... February 12, 2016 , ... ... of the Pittsburgh metro area, celebrates the beginning of the latest charity campaign ... develop social skills through art. Donations to this worthy cause are currently being ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... , Maharashtra, February 12, 2016 ... Market research report titled Chronic Inflammation Global Clinical ... a snapshot of the global clinical trials landscape ... clinical trials by Region, Country (G7 & E7), ... point status and reviews top companies involved and ...
(Date:2/11/2016)... 2016 Laboratory glassware and plasticware ... These may range from microscope slides to large storage ... from borosilicate glass because of its low weight and ... hand, started gaining popularity over the past decade when ... glass with plastic in several applications due to its ...
(Date:2/11/2016)... 2016 Potrero Medical, Inc., the developer of the ... appointment of George M. Rapier, III , MD, to ... , WellMed is one of the nation,s largest physician ... members in Texas and ... his own internal medicine practice, he has been instrumental to ...
Breaking Medicine Technology: