Scientists led by Prof Mark Anderson from the University of Iowa have found that the enzyme CaMKII (Calcium/calmodulin-dependent kinase II), known for its role in heart arrhythmia, is linked to the harmful effects of oxidation in the respiratory tract, triggering asthmatic symptoms.
Rendition of CaMKII in the closed conformation (Curtis Neveu / CC BY-SA 3.0)
“The finding could lead to the development of a drug that would target the CaMKII enzyme,” said Prof Anderson, who with colleagues reported the finding in the journal Science Translational Medicine.
“Current treatments don’t work well. It’s a kind of an epidemic without a clear, therapeutic option. The take-home message is that inhibiting CaMKII appears to be an effective anti-oxidant strategy for treating allergic asthma.”
Prof Anderson with colleagues knew from previous work that the CaMKII enzyme played a role in the oxidation of heart muscle cells, which can lead to heart disease and heart attacks. They surmised the same enzyme may affect oxidation in the respiratory system as well.
They first tested the enzyme in airway muscle cells, but to little effect. They then tried to block the enzyme in the airway lining (epithelial) cells. They noticed that mice with the blocked enzyme had less oxidized CaMKII, no airway muscle constriction and no asthma symptoms. Similarly, mice without the blocked enzyme showed high ‘oxidative stress,’ meaning lots of oxidized enzymes in the epithelial cells, a constricted airway and asthma symptoms.
“The study suggests that these airway lining cells are really important for asthma, and they’re important because of the oxidative properties of CaMKII. This is completely new and could meet a hunger for new asthma treatments. Here may be a new pathway to treat asthma,” the scientist said.
The researchers also took tissue samples from the airways of patients with asthma. True to their hypothesis, they found more oxidized enzymes in those patients than in healthy individuals.
Taking a step further, the team found that mild asthma patients who inhaled an allergen had a spike in oxidized CaMKII in the epithelial cells just a day later.
“We have this very compelling association. More studies in patients are needed to validate the approach,” Prof Anderson concluded.
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Bibliographic information: Philip N. Sanders et al. 2013. CaMKII Is Essential for the Proasthmatic Effects of Oxidation. Sci Transl Med, vol. 5, no. 195, p. 195ra97; doi: 10.1126/scitranslmed.3006135
