Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Studies define biochemical structure that keeps blood pressure low, bypass grafts open

16.08.2002


A sort of biochemical scaffold for a compound that enables blood pressure to be low, heart bypass grafts to remain open and nerves to communicate has been identified by Medical College of Georgia researchers.


Dr. Richard C. Venema (left) and Dr. John D. Catravas have received American Heart Association and National Institutes of Health funding to study a biochemical scaffold they have discovered that helps keep blood pressure low and heart bypass grafts open.


A process called co-localization looks for the presence of two key proteins in the scaffold the researchers found; the antibody for heat shock protein 90 is labeled green and the one for sGC is labeled red. The yellow images show the proteins are found together in the living endothelial and smooth muscle cell. The left side shows the proteins in the endothelial cell and the right shows a smooth muscle cell.



Researchers say identifying the framework for how these and other very positive health benefits occur should help them find ways to augment the benefits and identify new treatments for cardiovascular disease, which may result when the support structure falls apart.

"It’s a whole new ball game," Dr. John D. Catravas, director of the Vascular Biology Center, said of the findings which contradict previous understanding of how the compound, cyclic GMP, which also helps keep blood vessels open and enables penile erection, is ultimately produced.


Dr. Catravas and Dr. Richard C. Venema, biochemist and molecular biologist, recently received funding from the American Heart Association and the National Institutes of Health to study how the scaffold they have found is assembled.

They found the scaffold while studying the endothelial and smooth muscle cells – the two major cell types within blood vessels – in the vessels of healthy animals. They found, not surprisingly, nitric oxide synthase which makes nitric oxide, the short-lived gas that, in turn, activates the enzyme guanylate cyclase or sGC, an enzyme key to the production of cyclic GMP; in fact, heart drugs such as nitroglycerin work by stimulating sGC to produce cyclic GMP.

They also found the heat shock protein 90, or hsp 90, – one of the ubiquitous heat shock proteins – which makes nitric oxide synthase more efficient in producing nitric oxide.

What they didn’t expect was to find that the three substances combined to form an efficient biochemical structure that makes sGC readily available to support the positive benefits of cyclic GMP.

Prior to the findings by MCG researchers, it was believed that only hsp 90 and nitric oxide synthase were packaged together, that the resulting nitric oxide would essentially float away in search of sGC. But in fact, that may be the disassembled structure that can precipitate or augment cardiovascular disease, Dr. Catravas said.

"The way we think it works right now is that this hsp 90 is like a scaffold that allows sGC and nitric oxide synthase to attach," Dr. Catravas said. "You have one nitric oxide synthase sitting on the hsp 90 and you have an sGC molecule, which allows for a very, very close environment for the nitric oxide to move to the sGC. This is very important because nitric oxide has a very short life and there are other compounds inside cells that, as soon as the nitric oxide is produced, they grab it and either inactivate it or turn it into a toxic compound."

And there’s the rub. When sufficient nitric oxide isn’t available to activate sGC, the unhealthy result can be production of one of the most potent self-made toxins in the body and resulting hypertension, heart and kidney disease and erectile dysfunction. "We propose that when the enzyme sGC is not part of the structure, this contributes to cardiovascular disease," Dr. Catravas said.

"We are saying that one of the reasons nitric oxide is more beneficial than detrimental in the body is because it doesn’t have the opportunity to be attacked by other compounds and become a toxin because it’s very close to its receptor, to the sGC enzyme that it stimulates and then creates all the good things that it does," he said.

They first confirmed the structure by using a process called immunoprecipitation, in which antibodies were used to try to pull each of the three proteins out of the scaffold, Dr. Venema said. "When we pulled down heat shock protein 90, for example, it also pulled down sGC and nitric oxide synthase because they are all attached."

An NIH grant reviewer wanted to know if this union held up in an intact, living cell as well, rather than in a cell that is ground up for the purposes of immunoprecipitation where a chemical reaction could explain the close proximity of sGC.

So they used a process called co-localization to also study the relationship in a living cell, using fluorescent antibodies to the two proteins: the antibody for hsp 90 was labeled green and an antibody for sGC was labeled red. The resulting yellow glow showed that the two proteins were together in the living endothelial and smooth muscle cell.

The question remained: Does the form they found really affect function? So they also used drugs to interfere with the scaffolding and the activity of the sGC enzyme decreased. "That is when we started thinking we had something important," Dr. Catravas said.

Now they are looking to see exactly where hsp 90 and sGC bind and why sometimes they don’t; possibly a mutation in heat shock protein 90 makes it difficult for the other two proteins to attach, they said.

"This is the hypothesis: when these two proteins move apart, that is when you worsen or precipitate cardiovascular disease. We still have to prove this," Dr. Catravas said. "If this is true, it could very well change how we treat those diseases."


###
American Heart Association and National Institutes of Health funding

Toni Baker | EurekAlert!

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>