Researchers discover how nitric oxide regulates death switch in cells

Researchers in NUS discover how nitric oxide protects brain cells from dying

A team at NUS led by Dr Jeffrey Armstrong and Associate Professor Matthew Whiteman, both from the Department of Biochemistry, has scored a first in the research of nitric oxide and how it functions in the human body.

Nitric oxide is a free radical gas with a diverse range of cellular action. Free radical seems to be a bad word these days - associated with causing havoc in our body. However it is something we live with -- our immune system produces free radicals to fight invading bacteria and viruses and cells use free radicals to communicate with each other.

But is nitric oxide all bad? As early as 1999, researchers from Harvard University have shown that nitric oxide protected brain cells from dying after they had lost their anti-oxidant defences. But nobody knows exactly how nitric oxide controls the "death switch" in cells -- till Dr Armstrong and his team uncovered the mystery recently, discovering the mechanism behind the process.

They found that nitric oxide reacts with mitochondrial proteins (mitochondria are structures in human cells that turn nutrients into energy) -- it blocks the "switch" in these proteins which kill cells after they have lost their anti-oxidant defences. It works by binding to these sites and blocking the death signals.

Dr Armstrong cited the example of how nitric oxide is over-produced in some cancer cells, blocking the activation of the switch mechanism and hence preventing cells from dying. This may lead to tumour formation and progression and is one situation where the over production of nitric oxide is not a good thing.

The flip side of the coin is that sometimes, increased production of nitric oxide may be good for us. Dr Armstrong explained that as nitric oxide can prolong cell life, it may be an effective way to treat certain neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease where cells die prematurely.

Dr Armstrong hopes that the findings of the research will help shed more light in one of his studies -- the pathology that occurs in endothelial cells (cells lining the interior of blood vessels) in diabetes. Nitric oxide acts on the endothelial cells, relaxing them so that blood can pass through. With the help of a Biomedical Research Council grant, he will be examining the role of nitric oxide in the various complications associated with Type 2 Diabetes, for example, heart disease, kidney damage as well as blindness.

Added Associate Professor Whiteman: "Nitric oxide keeps our blood vessels dilated. One topical example is the drug Viagra which acts by increasing the effectiveness of nitric oxide making it work where it counts. However in certain human diseases the body loses control of nitric oxide production resulting in either too much or not enough being made. From our research, we can learn to balance the production of nitric oxide in our body."

Associate Professor Whiteman was a winner of the 2004 Faculty of Medicine's Outstanding Researcher Award as well as the 2003 Office of Life Sciences Young Investigator Award. One of his research interests is the mechanisms of cartilage cell death in inflammatory and degenerative joint disease, processes mediated by nitric oxide.

Since getting together in July 2003, the "dynamic duo" has published more than 10 papers in tier one journals. Dr Armstrong will also be presenting their work on nitric oxide at the Molecular and Cellular Bioenergetics, Gordon Research Conference at The University of New England (26 June to 1 July, 2005).

The duo hopes that through collaborating with clinicians, their research could lead to a new protein, perhaps an anti-oxidant compound that can delay adverse changes in our body.

Published: 12 Jul 2005

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