In this study, just published in Circulation Research, researchers at Boston University School of Medicine have demonstrated for the first time that short elevations in circulating levels of this simple anion are sufficient to have a lasting impact on the heart by modulating its oxidation status and its protein machinery.
Nitrite, an oxidation product of the ubiquitous short-lived cell signaling molecule, nitric oxide (NO), was until recently thought to be biologically inert at the relatively low levels found in the body. Traces of nitrite are present in our diet and significant amounts are continuously produced from nitrate, another oxidation product of NO and a constituent of green, leafy vegetables. The suspicion that high levels of nitrite and nitrate may cause cancer, as well as concerns about their risk to compromise the ability of red blood cells to deliver oxygen to tissues, have led to strict regulations aimed at limiting our exposure to these substances through drinking water and food products.
In the past few years, however, multiple research groups have shown that low concentrations of nitrite exert numerous beneficial effects, ranging from anti-bacterial activities to increases in local blood flow, and that they can somehow protect tissues from damage when oxygen is suddenly cut off and then rapidly restored, as occurs during heart attacks and strokes.
To study the molecular underpinnings of this protective effect of nitrite, the researchers at Boston University School of Medicine used a rat model in which they administered nitrite only once, causing a short spike in circulating levels, as a way to simulate the types of naturally occurring increases in nitrite that follow exercise or consumption of a meal rich in nitrate.
The researchers used a systems-biology approach in which changes in multiple biological and biochemical systems (e.g., the composition of a large number of proteins, the concentration of several small molecule metabolites, and functional outcomes) are simultaneously monitored and then integrated to produce one final picture in order to provide a broader view of the impact of this treatment on the heart. They tested their theory that following these changes over time and at different doses of nitrite might help to explain the protective effects of nitrite on the heart.
"What we found was that a single brief nitrite treatment elicited persisting changes in the heart's oxidation status together with lasting alterations to numerous proteins involved in the heart's energy metabolism, redox regulation, and signaling," said David H. Perlman, a post-doctoral research associate in the Cardiovascular Proteomics Center at Boston University School of Medicine, and lead author of the study. "These alterations were particularly striking because they persisted at least 24 hours after the actual nitrite levels had returned back to normal, and they were correlated strongly with the improvements in heart function observed at the same time."
He noted that this type of protection, called 'cardiac preconditioning', is a recently discovered phenomenon shown to be caused by numerous pharmacological agents.
"The proteins we have implicated include some key proteins, such as mitochondrial aldehyde dehydrogenase, that have been shown by others to be critical to cardiac protection afforded by other agents and triggers," added Perlman. "This is exciting because it ties nitrite-triggered cardioprotection into the broader preconditioning field. Our study complements and extends other work, and identifies new players of potential importance for protection of the heart."
Perlman explained that nitrite levels in our bodies change under a number of circumstances, such as when we run up a flight of stairs or eat a big serving of salad.
"For years, the resulting bursts in nitrite were considered to be of little if any physiological relevance. Now we have good reason to believe that even small spikes in nitrite concentration can alter protein function in the heart in ways that afford protection," noted Perlman.
"We are intrigued by the breadth and magnitude of the proteomic changes in heart mitochondria elicited by a single, short-lasting elevation in nitrite concentration and believe that our findings will have broad implications for mitochondrial signalling and cardiac energetics," commented Martin Feelisch, senior author of the study. "It looks as though nitrite is triggering an ancient program aimed at fine-tuning mitochondrial function. Although the present study focussed on the heart, our observations may extend to other tissues and translate into relevant changes in muscle function elsewhere. If true, this may help explain, for example, the training effects of very short periods of exercise, which are known to be associated with elevations in circulating nitrite concentrations."
Interestingly, only low and high doses of nitrite, but not those in-between, were found to be protective. Although further studies will be needed to fully delineate the mechanisms of nitrite-induced cardioprotection, this study informs ongoing basic and translational studies by highlighting the importance of the dose-effect relationship for nitrite and the broad array of downstream targets possibly involved in its cardioprotective efficacy, the researchers concluded.
Gina DiGravio | EurekAlert!
Further reports about: > Circulation Research > Medicine > Stress > biochemical systems > blood cell > cardiac preconditioning > food products > heart attacks > key protein > leafy vegetables > nitric oxide > nitrite-triggered cardioprotection > oxidation product > oxidation status > spikes in nitrite
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy