New method for preventing oxidative damage to cells: Findings could lead to enhanced health supplements, progress on Parkinson's

ScienceDaily (Dec. 2, 2010) — The discovery by UCLA biochemists of a new method for preventing oxidation in the essential fatty acids of cell membranes could lead to a new class of more effective nutritional supplements and potentially help combat neurodegenerative disorders such as Parkinson's disease and perhaps Alzheimer's.

While polyunsaturated fatty acids are essential nutrients for everything from brain function to cell function, they are the most vulnerable components in human cells because of their high sensitivity to oxidative modifications caused by highly reactive oxygen molecules in the body.

The biochemists, led by UCLA chemistry and biochemistry professor Catherine Clarke, have developed a new method for increasing the stability of polyunsaturated fatty acids. They have discovered a way to make these molecules harder to break apart so that oxidation is less likely to occur, rather than relying on antioxidants to repair damage after it occurs.

"These compounds (polyunsaturated fatty acids) are so important, yet so fragile," Clarke said. "In many diseases, cell membrane function deteriorates, and it's exciting to think an enhanced class of supplements may be able to correct neurodegenerative diseases, and perhaps even oxidative stress-related aging. It would be a new strategy to treat and reinforce the molecule at the place where it is most prone to damage, instead of taking more antioxidants. This could be a new approach to battling diseases resulting from oxidative stress.

"Our research highlights how vulnerable these essential polyunsaturated fatty acids are," she said. "They are so readily damaged. Many neurodegenerative diseases, such as Parkinson's disease and perhaps Alzheimer's disease, are tied to oxidative stress."

Polyunsaturated fatty acids are also used to produce a huge array of fatty acid-derived hormones that mediate pain, inflammation and blood clotting.

The research, federally funded by the National Institutes of Health, is published in the online edition of the journal Free Radical Biology and Medicine, a major source for research on oxidative stress, and is scheduled for publication in a 2011 print edition.

In the research, Clarke and her colleagues show that polyunsaturated fatty acids can be strengthened by replacing their most vulnerable hydrogen atoms, which are easily stripped away, with much more stable deuterium, an isotope of hydrogen with one extra neutron. The result is the creation of a fatty acid that serves the same function as its predecessor, but without the same susceptibility to oxidation.

The biochemists also describe applying this reinforcement process to two essential dietary fatty acids and show that yeast cells treated with the reinforced polyunsaturated fatty acids are much more resistant to oxidative stress than yeast treated with normal polyunsaturated fatty acids.

"You can think about polyunsaturated fatty acids like an oil-based paint," Clarke said. "When you spread the oil-based paint on the wall, it turns into a hard coat of enamel. That happens because of an oxidation reaction. A hard coat of enamel is great for a wall but lousy for a cell membrane. Cells have to deal with damage continually and have to be able to repair the damage that results from the oxidation."

Clarke's research team included four UCLA undergraduates: lead author Shauna Hill, who worked in Clarke's laboratory as many as 70 hours a week and earned a bachelor's degree in biochemistry in June; Bradley Kay; Vincent Tse; and Kathleen Hirano, who graduated from UCLA in 2009 with a bachelor's in biochemistry and is now a graduate student at UC Berkeley.

The researchers conducted experiments with a strain of yeast specially modified to lack antioxidants. They found that colonies treated with normal, naturally occurring polyunsaturated fatty acids died quickly, while those treated with the deuterium-reinforced fatty acids displayed resilience on par with wild, unmodified yeast. The replacement of a few hydrogen atoms with deuterium meant the difference between a rapid death and vigorous life for the yeast samples.

"Shauna, with Kathleen, Bradley and Vincent, tested fatty acids in yeast mutants that lacked the antioxidant coenzyme Q, where we know they are very sensitive to stress," Clarke said. "What they showed is that when the yeast were treated with the isotopically reinforced fatty acids, they were fine, but when the yeast were treated with standard polyunsaturated fatty acids, 99 percent of them died in just four hours."

"We tested the viability of yeast -- with the hydrogen atoms -- that lacked the antioxidant coenzyme Q, and our test showed that they were not able to survive," Hill said. "However, wild, normal yeast with coenzyme Q were able to grow, and survived."

The researchers then replaced four hydrogen atoms with four heavy deuterium hydrogen isotopes.

"The difference was enormous," Hill said. "We were really surprised that the heavy isotopes had such a drastic effect."

"Initially, I did not believe the results were correct," said Beth Marbois, a UCLA research chemist and co-author on the research. "But they were."

Yeast normally do not have these fats but will absorb both the normal and the isotope-reinforced fatty acids without preference when they are presented in solution, Hill and Marbois showed.

Other co-authors of the research included Mikhail Shchepinov, chief scientific officer of Retrotope Inc. in Los Altos Hills, Calif., and Dragoslav Vidovic from the department of chemistry at England's Oxford University.

The human body is unable to make polyunsaturated fatty acids such as omega-3 fatty acids and omega-6 fatty acids. Many people buy supplements such as fish oil, omega-3 fatty acids or flaxseed oil to get and preserve these nutrients. However, when a polyunsaturated fatty acid is oxidized, a hydrogen atom is stripped away from the molecule, causing it to form a new compound with the oxygen in the blood stream that impairs the function of the cell membrane.

Olive oil, walnut oil and flaxseed oil have some of the essential fats that we need for brain function, retina function and other critical body functions. Neurons in the brain and heart and in muscle cells have large amounts of these essential fats. Salmon has them because the fish eat microorganisms in the ocean that generate these fats.

Fish oil has 10 hydrogen atoms that are vulnerable and could be reinforced to be made less likely to degrade, Clarke noted.

Reinforced polyunsaturated fatty acids potentially could create membranes that are at least somewhat resilient to oxidative damage, Clarke said.

After one polyunsaturated fatty acid molecule is damaged, a chain reaction ensues as the adjacent fatty acids throughout the membrane become similarly degraded. What was once a semi-permeable barrier that regulated cell function becomes a rigid lattice of cross-linked fatty acids that prevents the cell from achieving its purpose -- which could be anything from synthesizing a protein to sending a signal to the nervous system.

Antioxidants, found naturally in many types of berries and available in supplements such as vitamin E, target the gaps left in molecules when a hydrogen atom is removed through oxidation. The antioxidants quench the reactive oxidized lipids, forming a new compound that prevents the molecular degradation from spreading to its neighbors.

The start of the oxidation chain reaction in a cell membrane is like a house on fire, where the antioxidants are the firefighters that work to extinguish the blaze before it spreads to nearby homes. Because a deuterium atom has twice the mass of a hydrogen atom, the carbon-to-deuterium bond in the modified fatty acid is much stronger than the carbon-to-hydrogen bond in the naturally occurring version. Thus, a fatty acid reinforced with deuterium acts like a home with fire-retardant materials that make it difficult for the first spark to ignite. Ideally, no firefighters -- or antioxidants -- are needed.

Antioxidants are like a mop-up crew, Clarke said. After the hydrogen atoms are pulled off, antioxidants stop the harmful chain reaction. Using another analogy, Clarke said, "Instead of taking an antioxidant to jump in front of a bullet, you place bullet-proof vests on the hydrogen atoms."

While wild yeast are resistant to oxidation at room temperature, they do begin to experience stress as the temperature rises. At high temperatures, wild yeast colonies treated with deuterium-reinforced polyunsaturated fatty acids show much greater resilience than those treated with unmodified fatty acids -- a result that indicates that even cells with integrated antioxidant mechanisms can benefit from the addition of deuterium-enhanced fatty acids, Clarke said.

Eat fish and stay physically active

UCLA's Marbois recommends eating fish frequently, especially fatty fish such as salmon, and staying physically active.

"Scientists who conduct aging research know that the one critical characteristic of people who live very long lives is not taking nutritional supplements but staying physically active," she said.

If you take fish oil, Marbois advises, keep the container in the refrigerator. "At room temperature, they will oxidize and degrade at a faster rate than in the refrigerator," she said.

Both Clarke and Marbois praised the student researchers.

"It's a real privilege to work with these students," Marbois said. "The undergraduates here constantly amaze me."

Clarke described working with the students as "fantastic, so much fun."

The students returned the praise of their mentors.

"Working in Professor Clarke's laboratory has been a life-changing experience for me," said Hill, who is applying to graduate schools in biochemistry and cellular and molecular biology. "If it weren't for this lab, I don't know if I would be applying for grad schools right now."

"Conducting research in Professor Clarke's laboratory is an amazing opportunity," Tse said. "Friends at other universities have a hard time working in laboratories, but at UCLA, the opportunities are here for us, and I feel privileged to be able to do this research."

"I wish I got involved in research earlier; it's so interesting and rewarding," Kay said.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of California - Los Angeles. The original article was written by Stuart Wolpert and Kim DeRose.

Journal Reference:

Shauna Hill, Kathleen Hirano, Vadim V. Shmanai, Beth N. Marbois, Dragoslav Vidovic, Andrei V. Bekish, Bradley Kay, Vincent Tse, Jonathan Fine, Catherine F. Clarke. Isotope-Reinforced Polyunsaturated Fatty Acids Protect Yeast Cells from Oxidative Stress. Free Radical Biology and Medicine, 2010; DOI: 10.1016/j.freeradbiomed.2010.10.690

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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Vaccines could help what's ailing fish

ScienceDaily (Oct. 26, 2010) — U.S. Department of Agriculture (USDA) scientists are developing vaccines to help protect healthy farm-raised catfish against key diseases.

Working as a team, microbiologist Phillip H. Klesius and molecular biologists Julia Pridgeon and Craig Shoemaker with USDA's Agricultural Research Service (ARS) at the agency's Aquatic Animal Health Research Unit in Auburn, Ala., and Joyce J. Evans, aquatic pathologist at the Auburn unit's lab in Chestertown, Md., are developing vaccines against Streptococcus iniae, S. agalactiae and other pathogens.

ARS is USDA's principal intramural scientific research agency. This research supports the USDA priority of promoting international food security.

The scientists modify the genetic makeup of pathogens to make them nonvirulent, and then develop vaccines that expose fish to low doses of the modified forms of the pathogens.

Klesius and Pridgeon have developed a modified live S. iniae vaccine that appears to be superior to inactivated or killed vaccines. The live modified vaccine has enough similarity with the pathogen to create a lifelong immunity in fish, according to Klesius.

Scientists are looking at new methods to vaccinate fish. But for now, the vaccination process consists of immersing the fish in water that contains the modified pathogen.

Previous research breakthroughs have benefited the catfish industry. For example, a ARS-developed vaccine against the pathogen Edwardsiella ictaluri, which causes enteric septicemia, has been widely adopted by fish growers.

In an earlier trial, the vaccine against enteric septicemia of catfish was tested by Mississippi State University researchers. Results showed a 12 percent increase in the survival rate of fish that were given the vaccine, and a substantial increase in returns for producers who used the vaccine in their ponds.

Read more about this and other research on aquaculture in the October 2010 issue of Agricultural Research magazine at: http://www.ars.usda.gov/is/AR/archive/oct10/fish1010.htm

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by USDA/Agricultural Research Service. The original article was written by Sandra Avant.

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Birds could signal mass extinction

ScienceDaily (Oct. 12, 2010) — The first detailed measurements of current extinction rates for a specific region have shown that birds are the best group to use to track the losses. The study also reveals Britain may be losing species over ten times faster than records suggest, and the speed of loss is probably increasing: the losses from England alone may exceed one species every two weeks.

The study, by Oxford University researchers, shows that many types of obscure organism in Britain are going extinct at the same rate as the birds -- evidence supporting fears of a global mass extinction. A report of the research is published in an upcoming issue of the journal Biological Conservation as countries prepare to meet in Japan 18-29 October to discuss biodiversity conservation targets.

'Biodiversity loss is arguably much more serious and more permanent than climate change,' said Clive Hambler of Oxford University's Department of Zoology, lead author of the research. 'But it's impossible to know if policy targets to reduce the loss are being met without accurate measures of extinction rates. Until now, we had only crude estimates for a very few types of organism. Now we've got evidence that many groups of living things -- lichens, bugs, moths, fish, plants and so on -- are going extinct at a very similar rate to the birds.'

Using Britain's uniquely detailed natural history records, the researchers found that 1-5% of the region's species in many groups were lost since 1800, with higher losses in the Twentieth Century compared to the Nineteenth. Using further data from the USA and across the whole globe, the researchers show that the patterns of extinction in Britain are likely to be typical of those found on land and freshwater elsewhere.

Mr Hambler said: 'The birds are beautiful creatures, but they are also diverse, and many of them are specialised to particular habitats. This makes them sensitive to changes in their environment -- such as loss of mature trees, or the drying out of swampy ground, or coastal development. And what makes them really special for monitoring extinction is that they are also exceptionally easy to study, anywhere in the world -- so we can detect declines in their populations long before we notice losses of the more obscure things like slime moulds or mosses. It's no coincidence they can signal environmental change.'

'The underlying reason for the similarity of extinction rates in birds and the other living things is that habitat loss affects them in the same way. Our work supports the use of birds to indicate extinction rates in Britain, the USA and globally, and they should now be tried in places such as tropical forests where the bulk of other species will never be recorded.'

'The recorded extinctions in any region are just the tip of the iceberg, because there are not enough observers,' said Mr Hambler. For example, in March this year the British government's advisory body, Natural England, reported about 500 species lost from England since 1800. 'The losses reported by Natural England are under 0.5% per century, from England's 55,000 species,' notes Mr Hambler. 'Our research suggests that the actual losses could be over ten times this number, with about one species going extinct in England every fortnight.'

Natural England also reported species losses in England had apparently declined in recent decades, but the Oxford study suggests that this is not the case. Hambler and colleagues found there are about 1000 endangered species on the brink of extinction in Britain -- indeed many of these may already be extinct.

'People tend to be hesitant in declaring extinction, which leads to problems assessing the current rate,' said Mr Hambler. 'Many ancient and important habitats in Britain are threatened today because of human activity and population growth -- whether it's an increase in water use, growing use of wood fuel, or the growth of urban sprawl. Despite conservationists' efforts it's very likely extinction rates will continue to rise in Britain and globally for many years. These losses will impact on human welfare, and I'd say conservation needs a profile and resources even bigger than climate change.'

Alongside studies of birds, the researchers believe that recording rates of habitat loss will provide a good, simple measure of some elements of biodiversity loss.

Mr Hambler said: 'This work strengthens the claim that the world is suffering a mass extinction. We can now be much more confident that across the planet the less conspicuous and less well-known species are going extinct at a similar high rate to that already witnessed in birds, fish and amphibians.'

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Oxford.

Journal Reference:

Clive Hambler, Peter A. Henderson, Martin R. Speight. Extinction rates, extinction-prone habitats, and indicator groups in Britain and at larger scales. Biological Conservation, 2010; DOI: 10.1016/j.biocon.2010.09.004

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New insights could mean better fish feeds

ScienceDaily (Aug. 17, 2010) — A better understanding of what happens in a fish's body when it eats could lead to the production of better fish feeds. Researchers at the University of Gothenburg, Sweden, are hoping to contribute to more energy-efficient aquaculture. In the long term, this could increase the supply of farmed fish and so provide more food for the Earth's burgeoning population.

Studies of fish by researcher Henrik Seth from the University of Gothenburg's Department of Zoology have helped to increase our understanding of what happens in parts of the body after one of its most frequently recurring activities: eating.

It has long been known that a number of changes take place in the body following food intake, including an increase in blood flow to the stomach and intestines. This happens in humans and other mammals as well as in fish. However, we still know relatively little about the signals that trigger these changes and how they are regulated. Both the volume and the chemical composition of food play a role in how the body reacts.

Chemical composition affects energy consumption

"It's not just blood flow that is affected by its chemical composition, but also energy consumption in the stomach and intestines, and these factors are believed to be interlinked," says Seth.

If energy consumption in the stomach and intestines rises, an increased blood flow will be needed to supply the active tissue with oxygen and nutrients.

"Increased blood flow is also important for carrying away absorbed nutrients so that they can be used to nourish different parts of the body and to build up and repair different tissues."

The results of Henrik Seth's research also show that parts of a fish's nervous system are involved in this regulation, and that a number of hormones (including cholecystokinin) can affect this regulation depending on the composition of the food.

It is primarily here that an increased understanding of this field could make it possible to produce fish feeds in the future that require less energy to be broken down and absorbed.

"It might then be possible to enhance the growth of farmed fish, which would greatly increase the efficiency of fish farming with less wastage of energy," says Seth. "Using nutrients as efficiently as possible may prove increasingly important as the global population continues to swell."

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Gothenburg, via EurekAlert!, a service of AAAS.

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