A highlight of myoglobin diversity: the nitrite reductase activity during myocardial ischemia-reperfusion.
Myoglobin, famous as an important intracellular oxygen binding hemeprotein, displays a variety of functions. The first pioneering review on myoglobin was published as early as 1939, in which Millikan concluded that "muscle hemoglobin" acts primarily as a short-term dioxygen store, tiding the muscle over from one contraction to the next. Since that time, myoglobin has become one of the most widely studied proteins in a variety of research fields ranging from chemistry to medicine. Recently it was discovered that in the heart myoglobin changes its function in dependence of oxygen tension, acting as an oxygen sensor. Under normoxic conditions myoglobin plays the role of a nitric oxide (NO(*)) scavenger, protecting the heart from the deleterious effects of excessive NO(*). During hypoxia however, myoglobin changes its role from an NO(*) scavenger to an NO(*) producer. Deoxygenated myoglobin reduces nitrite to bioactive NO(*). The produced NO(*) downregulates the cardiac energy status and reduces myocardial oxygen consumption, thus protecting the heart. Myoglobin also exhibits a nitrite reductase function under further pathophysiological conditions. During myocardial reperfusion after ischemia, myoglobin - via nitrite - regulates respiration and cellular viability. This leads to a dramatic reduction of myocardial infarct size and to an improvement of myocardial function. The reaction between myoglobin and nitrite thus seems to play an imminent role in the regulation of cardiac function in physiology and pathophysiology.
Hendgen-Cotta
Ulrike B
UB
Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, Düsseldorf, Germany.
Kelm
Malte
M
Rassaf
Tienush
T
D000818:Animals; D002470:Cell Survival; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D009572:Nitrite Reductases / Q000378:metabolism*
D009211:Myoglobin; D009572:Nitrite Reductases