New insight into cell death could help fight heart disease

Posted on March 18, 2014

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Dr Poon: ‘The faster the body can clear away dead cells in the cholesterol plaque on the walls of our arteries, the more we can slow plaque progression and reduce the impact of one of Australia’s biggest killers.'

Dr Poon: ‘The faster the body can clear away dead cells in the cholesterol plaque on the walls of our arteries, the more we can slow plaque progression and reduce the impact of one of Australia’s biggest killers.’

La Trobe University research has shed new light on how dead and dying cells are removed from the human body.  The research could also lead to new ways to boost the body’s defence mechanisms and better treat a range of inflammatory diseases such as heart disease.

Cell biologist Dr Ivan Poon has been studying a protein called Pannexin 1 (PANX1), which is used by a dying cell to signal ‘defender’ white blood cells, or phagocytes, to find and remove that cell.

An immune cell (T cell) breaking apart during cell death.

An immune cell (T cell) breaking apart during cell death.

He’s discovered that the same protein is essential to cellular integrity and can control the ability of the dying cell to break into smaller ‘bite sized’ pieces, which can then be removed more efficiently by phagocytes. (See diagram, right.)

The discovery, which was made by Dr Poon in conjunction with colleagues at both La Trobe University and the University of Virginia, has been published in the latest issue of the leading scientific journal ‘Nature’.

Dead cell clean up essential

Dr Poon said more than two hundred billion cells die each day in the average adult human body as part of a normal turnover in various organs. He said it was essential to human health that they are removed quickly and efficiently.

‘The accumulation of unwanted dead and dying cells in the human body is linked to numerous disease states including inflammation and cardiovascular diseases, autoimmunity, cancer and infections, so it is vital that we better understand this process,’ Dr Poon said.

‘Now, for the first time, we have a much clearer understanding of the mechanisms of cell disassembly and removal that are taking place on such a massive scale in all of our bodies every day of our lives.

‘From here the next step could be to block the function of PANX1 protein using pharmacological compounds to encourage a greater number of dead and dying cells to break into smaller pieces.

Doing this is a bit like accelerating the demolition of the dying cell.

Impact on inflammatory disease

‘By further improving the efficiency of the body’s own “clean up” mechanism we can potentially reduce the impact of inflammatory diseases,’ Dr Poon said.

‘In the case of heart disease, the faster the body can clear away dead cells in the cholesterol plaque on the walls of our arteries, the more we can slow plaque progression and reduce the impact of one of Australia’s biggest killers.’

He said the work also had potential for improving critical broad-spectrum antibiotics, some of which currently have side effects ranging from inflamed tendons, central nervous system toxicity to, in rare ceases, death by liver toxicity.

‘It is still early days, but I hope this discovery will change the way scientists understand and mitigate common diseases that impact millions of people around the world.’

Dr Poon is based at the state-of-the-art La Trobe Institute for Molecular Science (LIMS) on the University’s Bundoora campus. His work is part of the University’s Research Focus Areas on understanding disease. – Tim Mitchell

Cell destruction during the experiment. Images here and above by Ivan Poon

Cell destruction during the experiment. Images by Ivan Poon

Invaluable findings for science and health care

An accompanying News and Views article in ‘Nature’ said: ‘In their groundbreaking paper Poon and colleagues demonstrated that rigorous molecular screening, when coupled with the power of observation in a well-regulated setting, can uncover surprising and invaluable findings.’

The article was written by Professor Christopher Gregory from Queen’s Medical Research Institute at the University of Edinburgh. It explained how programmed cell death – also known as apoptosis – was a ‘feature of normal life’, ensuring ‘the proper regulation of the size and quality of cells in tissues’.

Central role in cell death process

While much was known about the molecular mechanisms that trigger cell death, ‘it is unclear how dying cells are dismantled in a controlled manner once apoptosis is under way’, he said. However, this latest research demonstrated ‘a central role’ for the cell membrane channel PANX1 ‘in inhibiting cell disassembly during apoptosis’.

It also reported, unexpectedly, that ‘a member of a commonly prescribed class of antibiotic is able to modulate the activity of such channels,’ he added

Improved antibiotics

This could be relevant to improved antibiotic design, ‘especially for highly effective, broad-spectrum antibiotic such as Fluoroquinolones which can carry the risk of severe side effects for multiple organs, including liver failure’.

‘As always, the unexpected is the most fascinating,’ Professor Gregory concluded.

‘There is no doubt that this work will stimulate researchers in the seemingly disparate areas of apoptosis and antibiotics to find out more about PANX1 . The results may improve not only scientific understanding but also health care.’

Read the full News and Views article  (Link to come)