Navigation Links
Neural stem cells maintain high levels of reactive oxygen species, UCLA study finds

For years, the majority of research on reactive oxygen species (ROS) ions or very small molecules that include free radicals has focused on how they damage cell structure and their potential link to stroke, cardiovascular disease and other illnesses.

However, researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research have shown for the first time that neural stem cells, the cells that give rise to neurons, maintain high levels of ROS to help regulate normal self-renewal and differentiation.

The findings, published in the Jan. 7, 2011 issue of the journal Cell Stem Cell, may have significant implications for brain repair and abnormal brain development.

"Everyone thinks of ROS as things that kill cells, and they do," said Dr. Harley Kornblum, a professor at the Intellectual and Developmental Disabilities Research Center in the Semel Institute of Neuroscience and Behavior and senior author of the study. "Stem cells generally have been thought to maintain low levels of ROS to protect against damage, so our findings were surprising and we hope to be able to exploit this to promote neural repair and explore diseases such as autism and brain cancer."

The study also found that the neural stem cells were highly responsive to ROS stimulation, which increased their growth and differentiation. Conversely, diminishing cellular levels of ROS in the neural stem cells interfered with normal cell function in mice and in human and mouse cell lines.

"It wasn't just that neural stem cells maintained high ROS levels" said Janel Le Belle, an assistant researcher in Kornblum's lab and lead author of the study. "Changes in cellular ROS can affect how the stem cells function. This study could lead to an understanding of how elevated ROS due to environmental factors might play a role in brain overgrowth, such as occurs in some cases of autism."

The body has a system to make ROS when it needs it. Some cells, such as immune cells, surround bacteria or viruses and use ROS to kill the invading microbes. Outside influences such as stress and environmental factors such as exposure to radiation can increase ROS levels in cells.

Although ROS is produced by all cells in a passive manner as a by-product of normal cell metabolism, some cells also produce ROS in a directed manner using ROS-producing enzymes like NADPH oxidase (NOX). NOX-generated ROS can act as second messengers in tightly controlled signal transduction pathways for many growth and trophic factors. However, too much ROS damages and ultimately kills cells, so finding the correct balance is vital, Kornblum said. And in fact, when the neural stem cells in the study were given too much ROS, they did die.

Kornblum and his team also found that the ROS-mediated stem cell self-renewal and differentiation of these cells into neurons depended on a cell signaling pathway called PI3K/Akt, which is known to be involved in cellular functions such as cell growth, proliferation, differentiation, motility and survival. NOX-generated ROS affect PI3K/Akt signaling by causing the inactivation of the PTEN protein, an important tumor suppressor and negative regulator of the pathway, by oxidizing a cysteine residue in the protein, which inactivates its function.

Kornblum and his collaborators at UCLA, including Dr. Hong Wu, a professor of molecular and medical pharmacology and a co-author of the study, have been studying the PI3K pathway for years. The pathway is activated in some diseases, for example a subset of autism cases and in tuberous sclerosis, a rare, multi-system genetic disease that causes non-malignant tumors to grow in the brain and in other vital organs. The pathway also can be activated in certain cancers.

"One of our hypotheses is that in these disease states, for instance in autism, that in those with a genetic predisposition to PI3K activation, exposure to a stressor that increases ROS levels can exacerbate the predisposition, perhaps promoting the disease," Kornblum said.

In brain tumors, if the pathway gets activated in cells already susceptible to becoming cancerous, it may promote the proliferation of brain tumor cells or the propagation of brain tumors. Blocking the pathway, Kornblum said, may be one way to interrupt the malignant process.

Going forward, Kornblum and his team will seek to determine whether brain cancer cells use elevated ROS and the PI3K pathway to promote their own growth. Le Belle said they will also test whether elevated ROS during brain development can contribute to brain overgrowth in Autism. Additionally, the team will test to see if they can exploit the ROS-activated pathway to promote brain repair, for example, increasing the production of new neurons to replace damaged or dead neurons.


Contact: Kim Irwin
University of California - Los Angeles

Related medicine news :

1. Swiss agency approves clinical trial of UCI-created neural stem cell therapy
2. Neuralstem files FDA application for first drug therapy
3. How do neural stem cells decide what to be -- and when?
4. Neuralstem updates ALS clinical trial progress
5. Neuralstem chief scientific officer to take part in World Stem Cell Summit plenary session
6. Neuralstem stem cells survive and differentiate into neurons in rats with stroke
7. Misfolded neural proteins linked to autism disorders
8. The neural basis of the depressive self
9. Hurts so good -- neural clues to the calming effects of self-harm
10. Neuralstem files FDA application for first chronic spinal cord injury stem cell trial
11. Human neural stem cells restore motor function in mice with chronic spinal cord injury
Post Your Comments:
(Date:11/26/2015)... (PRWEB) , ... November 26, 2015 , ... Indosoft Inc., ... inclusion of an application server to improve system efficiency and reliability. , The new ... many of these standards, the system avoids locking itself into a specific piece of ...
(Date:11/25/2015)... ... November 25, 2015 , ... Medical ... once again for its stellar workplace culture with the company’s Cincinnati office being ... Medical Solutions’ Cincinnati office was named a finalist in Cincinnati Business Courier’s 13th ...
(Date:11/25/2015)... ... November 25, 2015 , ... For the first time, Vitalalert is ... One Beat ” campaign. The partnership between the two groups began in 2014 with ... International’s cause. , MAP International was founded in 1954 and is an international Christian-based ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... and athletic programs, launches new Wimbledon Athletics Facebook page to educate ... athletes for unsuspected cardiac abnormalities. About 2,000 people under the age of 25 ...
(Date:11/25/2015)... Calif. (PRWEB) , ... November 25, 2015 , ... Beddit® ... and Beddit Classic sleep tracking systems. The new app features a more intuitive SleepScore™ ... and understand how well you slept. The SleepScore is created by a proprietary algorithm. ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... 25, 2015  The American Academy of Pediatrics ... and the March of Dimes cheered today,s signature ... Infants Act of 2015 (S.799), which takes ... born exposed to drugs, such as opioids, and ... all three organizations have worked together leading advocacy ...
(Date:11/25/2015)...  Henry Schein, Inc., the world,s largest provider of ... and animal health practitioners, will unveil at the Greater ... ConnectDental® Pavilion , which brings together for the first ... to help any practice or laboratory enter the digital ... schedule of experts appearing at the Pavilion. --> ...
(Date:11/25/2015)... DUBLIN , Nov. 25, 2015 ... global pharmaceutical company, and Rugen Therapeutics, a start-up ... treatments for unmet CNS disorders and funded by ... that they have entered into an exclusive collaboration ... therapies for Autism Spectrum Disorders (ASD) and Obsessive ...
Breaking Medicine Technology: