Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

St. Jude researchers find key step in programmed cell death

03.03.2008
The discovery provides insight into how certain proteins, including Hax1, work and how they control the process of apoptosis

Investigators at St. Jude Children’s 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 paper’s 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 Kostmann’s 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 Parkinson’s 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 cytokines—small proteins used by neurons and blood-borne cells to communicate messages—contribute 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 mitochondria—tiny chemical packets that serve as the main energy source for cells. HtrA2 is made in the cell’s 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.

Carrie Strehlau | EurekAlert!
Further information:
http://www.stjude.org

Further reports about: Cytokine Hax1 HtrA2 apoptosis enzyme lymphocytes mitochondrial

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>