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
The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft
Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy