New findings about nitrovasodilators
Chest pain is the major symptom of patients with coronary heart disease. Agents that release nitric oxide (NO) within the body can help to treat such angina pectoris attacks because NO dilates arteries thereby improving blood circulation. To date, NO release from nitrovasodilators like glyceryltrinitrate is not fully understood. Pharmacologists in Bochum and Graz gained new insights into this process by analyzing the enzyme responsible for NO release. The results of this study have been published in the Journal of Biological Chemistry.
The reaction causing bioactivation is not well understood
So-called nitrovasodilators such as nitroglycerin have been used effectively in the treatment of angina pectoris in coronary heart disease for more than century. Within the human body, nitric oxide (NO) is released from the nitroglycerin and in turn stimulates an enzyme that dilates the arteries and thus improves blood circulation. In 1998, Robert F. Furchgott, Ferid Murad and Louis Ignarro were awarded the Nobel Prize for Medicine for their discoveries that nitric oxide is not only released from drugs but is being produced endogenously in the body and has an important function as a signalling molecule in the cardiovascular system.
The molecular mechanism of NO release
The positive effect of nitrovasodilators entirely depends on the release of NO or chemically related molecules within the vascular smooth muscle cells, the so called bioactivation. In 2002, Stamler and coworkers were able to identify mitochondrial aldehyde dehydrogenase-2 (ALDH2) as the enzyme responsible for bioactivation of nitroglycerin. ALDH2 is also involved in the decomposition of toxic metabolites of alcohol. Researchers from Bochum and Graz investigated the ALDH2-catalyzed bioactivation of nitroglycerin by exchanging amino acids to identify residues essential for NO release, thereby gaining insight into the catalyzed reaction. Dr. Michael Russwurm pointed out that a better understanding of bioactivation of nitrovasodilators at the molecular level is not only important for the therapeutic use of known NO donors, but also for the possible development of new NO-releasing agents. E.g. an altered bioactivation could reduce the well-known phenomenon of tolerance, i.e. the loss in efficacy of nitrovasodilators.
M. Verena Wenzl, Matteo Beretta, Antonius C. F. Gorren, Andreas Zeller, Pravas K. Baral, Karl Gruber, Michael Russwurm, Doris Koesling, Kurt Schmidt and Bernd Mayer: Role of the General Base Glu-268 in Nitroglycerin Bioactivation and Superoxide Formation by Aldehyde Dehydrogenase-2, The Journal of Biological Chemistry, Vol. 284, Issue 30, 19878-19886, JULY 24, 2009, doi:10.1074/jbc.M109.005652
Prof. Doris Koesling, Dr. Michael Russwurm, Department of Pharmacology and Toxicology, Medical Faculty of the Ruhr-University, 44780 Bochum, Germany, Tel. 0234/32-26827, -28397, E-Mail: Doris.Koesling@rub.de, Michael.Russwurm@rub.de
Editor: Meike Drießen
Dr. Josef König, | idw
3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg
Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
23.05.2018 | Life Sciences
23.05.2018 | Life Sciences
23.05.2018 | Physics and Astronomy