Alcohol busting enzyme reduces heart damage

Alcohol busting enzyme reduces heart damage

US scientists have discovered that an enzyme that breaks down alcohol can also protect heart tissue against damage by free radicals, for instance as a result of heart attack or surgery.

The study was the work of researchers at Stanford University School of Medicine in California, and the Indiana University School of Medicine in Indianapolis, and is published in the 12th September issue of the journal Science.

"We've found a totally new pathway for reducing the damage caused by free radicals, such as the damage that happens during a heart attack," said senior author Dr Daria Mochly-Rosen, a professor of chemical and systems biology at Stanford University School of Medicine.

Free radicals are highly unstable molecules that are necessary for many biological processes, but in their search to become stable, they can also cause undesirable damage to cells, including damage to heart tissue following heart attack or surgery.

The authors wrote in their background information that there is a lot of interest in developing drugs that limit the heart tissue damage that results from a heart attack or certain types of heart surgery. There was already evidence that heart muscle can be pre-conditioned to resist the damage caused by heart attack, and that moderate drinkers tend to have smaller and less severe heart attacks than teetotallers, but the underlying biology was still a mystery.

So Mochly-Rosen and colleagues decided to investigate an enzyme called aldehyde dehydrogenase 2 (ALDH2), which is involved in breaking down alcohol and has been linked with reduced heart tissue damage following heart attacks in rodents.

The researchers looked at the enzymes activated in heart attacks in rats that had been pretreated with alcohol and some that had not.

They found to their surprise that alcohol increased the activity of ALDH2 during heart attack by 20 per cent, and led to a 27 per cent drop in the associated damage.

Mochly-Rosen said that although the enzyme had been known about for some time, the researchers knew nothing about it except that it helped to break down alcohol in the bloodstream.

They were not expecting to find ALDH2 to be a key antioxidant fighting the free radicals. The enzyme works by neutralizing the toxins produced by alcohol, aldehydes. But these are also the same chemicals produced when free radicals react with fat molecules, and these are inside every cell.

"It's very easy for free radicals to find fat and oxidize it to aldehydes," explained Mochly-Rosen. Once the free radicals have turned fat into aldehydes, the aldehydes stick to DNA and other cellular matter and trigger unwanted processes that are thought to cause many diseases, including heart attack, Parkinson's and sun-induced skin ageing, said the researchers.

So the next step was to find a way to increase the activity of ALDH2. With the help Stanford High Throughput Bioscience Center they found a molecule that could do this. Alda-1 is a tiny molecule that reduced heart attack damage by 60 per cent in the rat model. Surprisingly, it works in an unexpected way: it protects ALDH2 from in turn being attacked by the aldehydes it removes.

Although Alda-1 has so far only been tested on rats, the researchers believe it has enormous potential in a range of applications, from reducing damage from heart surgery, to fighting hangovers, neurodegenerative diseases, and skin damage from the sun.

Another application could be to help people with a common mutation of ALDH2 that leaves them intolerant to alcohol and more susceptible to free-radical diseases. This mutation affects 40 per cent of people of Asian descent.

"Activation of Aldehyde Dehydrogenase-2 Reduces Ischemic Damage to the Heart."

Che-Hong Chen, Grant R. Budas, Eric N. Churchill, Marie-Hélène Disatnik, Thomas D. Hurley, and Daria Mochly-Rosen.

Science, 12 September 2008, Vol. 321. no. 5895, pp. 1493 - 1495.

DOI: 10.1126/science.1158554

Click here for Abstract.

Source: Science, Stanford University School of Medicine.

How to Reverse a Fatty Liver (Video Medical And Professional 2020).

Section Issues On Medicine: Cardiology