A poorly understood and previously unsuspected mechanism may be the key to understanding how lifestyle-associated forms of oxidative stress, such as exposure to cigarette smoke, damage cells in the lungs, reports the August 7, 2007, issue of PLoS One.
Toxins in cigarette smoke open unpaired hemichannels—small portholes in the cell surface—that can, with very little provocation, turn into major breaches in the cell’s integrity, leading to rapid cell death.
"Opening hemichannels allows stressful, often toxic, stimuli to flow directly into cells, overwhelming the delicate and carefully maintained balance within and triggering the signals that induce cell death," said study author Ratneshwar Lal, PhD, professor of medicine at the University of Chicago.
The mechanism behind hemichannel malfunction is believed to be the underlying factor in emphysema, which is brought on by smoking. Previous studies also found evidence of hemichannel malfunction in stroke victims.
Drugs that prevented hemichannels from opening protected the cells from similar exposures. Treating the cells with silencing RNA for the hemichannel protein also protected cells by preventing the creation of these channels.
"Improperly opened hemichannels may play a role in many other diseases tied to environmental stimuli," Lal said, "or even to normal aging, where oxidative stress is thought to contribute to the gradual accumulation of multiple small damaging hits. Finding and testing drugs or other mechanisms that can selectively block these unpaired channels offers a novel approach to disease prevention."