Researchers explore PKC role in lung disease

Researchers explore PKC role in lung disease
A JGP study examines the role of PKC in airway smooth muscle contraction and raises the possibility that this enzyme could be a therapeutic target for treating asthma, COPD, and other lung diseases. The diagram shown summarizes the pathways regulating airway smooth muscle contraction. Credit: Dixon, R.E., and L.F. Santana. 2013. J. Gen. Physiol.

New research examines the role of PKC in airway smooth muscle contraction and raises the possibility that this enzyme could be a therapeutic target for treating asthma, COPD, and other lung diseases.

In the lungs, pathological increases in the contraction of the (SMCs) lining airway walls—a process that decreases airflow—contribute to the chain of events leading to asthma and COPD, two common lung diseases. Jose Perez-Zoghbi and colleagues from Texas Tech University Health Sciences Center designed a series of experiments to investigate the role of the enzyme PKC in this process. The results, which appear in The Journal of General Physiology, provide new insight into the mechanisms involved in regulating luminal diameter of small airways and reveal PKC as a potential target for drug therapies.

The researchers used phase-contrast video microscopy, confocal microscopy, Western blot analysis, and pharmacological activators and inhibitors to investigate the role of PKC in airway SMC contraction in mouse lung slices. Their results suggest that activation of PKC in small airways promotes an influx of calcium into SMC and subsequent intracellular release of to generate low frequency SMC twitching. PKC activation also induces a strong calcium ion sensitization of contraction, eliciting a stronger contractile response to stimuli that increase free intracellular calcium. Consequently, activation downstream of various molecules, such as thrombin, that are present in the airways in conjunction with inflammatory , could sensitize the airway SMCs to contractile stimuli and contribute to the airway hyper responsiveness that is characteristic of asthma and COPD.

More information: Dixon, R.E., and L.F. Santana. 2013. J. Gen. Physiol. 141:161 Mukherjee, S., et al. 2013. J. Gen. Physiol. 141:165-178.

add to favorites email to friend print save as pdf

Related Stories

Calcium flow disruptions linked to heart failure

Jan 31, 2011

Excessive release of calcium inside cardiac muscle can cause sudden cardiac death in heart failure patients. New research has revealed how this could happen, opening up new possibilities for combating heart ...

Tweaking gene expression to repair lungs

Feb 25, 2013

A healthy lung has some capacity to regenerate itself like the liver. In COPD, these reparative mechanisms fail. HDAC therapies may be useful for COPD, as well as other airway diseases. The levels of HDAC2 ...

Recommended for you

Sierra Leone, Liberia brace for new Ebola cases

28 minutes ago

Two of the West African nations hardest hit by Ebola were bracing for new caseloads on Monday after trying to outflank the outbreak with a nationwide checkup and a large new clinic.

Reversing the effects of pulmonary fibrosis

50 minutes ago

Yale University researchers are studying a potential new treatment that reverses the effects of pulmonary fibrosis, a respiratory disease in which scars develop in the lungs and severely hamper breathing.

Streets bustling after Sierra Leone shutdown ends

7 hours ago

Streets in Sierra Leone's capital bustled again Monday after an unprecedented nationwide shutdown during which officials said more than 1 million households were checked for Ebola patients and given information ...

User comments