Death Defying Cells

 

“You can watch an individual cell shrivel up, look like it has no chance, and then come back to life,” says biological chemistry professor Denise Montell (center), with siblings Holly and Hogan Tang.

No one knows for sure what happens after death, but most of us can be relatively sure that once we’re dying, there’s no turning back.

A new Hopkins study suggests that it may be possible to do a 180 from dying — at least cells may be able to. When scientists exposed batches of cells to deadly poisons, the majority were still able to bounce back completely after those toxins were removed.

A better understanding of this death-defying process may offer some practical insight on how to save dying tissues after heart attacks or strokes, as well as prevent cancer in cells transiently exposed to toxins.

This new insight into death—or the lack thereof—got its start when Ho Lam “Hogan” Tang, a researcher in the lab of Hopkins professor Denise Montell, began his first year as a doctoral student at the Chinese University of Hong Kong. His main project was studying aspects of apoptosis, the process of programmed cell death.

While trying to figure out how the cell’s cytoskeleton, a network of fibers that helps it retain its shape, remolds during apoptosis, Hogan and his sister Holly Tang, a fellow researcher, became curious about whether the cells they exposed to toxins were really on an irreversible track to death.

In preliminary experiments, they waited until the cells appeared to be dying, then replaced the deadly brew with a nutritious broth normally used to grow cells. Within hours, most cells behaved as if they’d never faced mortality.

Montell, a professor in Hopkins’ Department of Biological Chemistry, was intrigued when she heard of this work. “There’s clearly some point when something is truly dead and can’t come back,” she says, “but there’s been a controversy about what constitutes the point of no return for cells.”

Hogan Tang headed for Montell’s lab in 2009 to continue his Ph.D., soon joined by Holly, who took a job as a lab coordinator. Together, the team, along with additional colleagues at Johns Hopkins, replicated the experiments performed in Hong Kong by exposing healthy cells from mice or rats that were growing in petri dishes to ethanol, a potent toxin. Within hours, the cells displayed the typical hallmarks of apoptosis. However, when the scientists washed the ethanol away, many of the cells regained aspects of their normal appearance. 

Their research showed that about 90 percent of the cells exposed to ethanol managed to survive. The team published their findings online in April in the scientific journal Molecular Biology of the Cell.

Repeat experiments showed that the ability to defy death could be universal for all or at least many kinds of cells in the body, Montell says. The experiments also showed that a small percentage of the surviving cells exposed to toxins developed some hallmarks of cancerous growth.

That finding could have implications for explaining and treating cancer, as well as other diseases, Montell says. For example, though researchers know that alcoholics have a propensity toward developing liver cancer, the reasons have been unclear. Based on this discovery, it’s possible that problem drinkers might continually bring their liver cells toward the brink of death and that some surviving cells continue on with genetic defects that lead to malignancy.

The results might also explain why cancer cells often develop resistance to chemotherapy. During chemotherapy, cells are transiently exposed to toxic drugs that induce apoptosis, and then the patient is allowed to recover. So while most of the cancer cells die, those that survive may develop genetic defects, some of which could contribute to their ability to resist death on the next round.

Montell, the Tang siblings and their colleagues plan to continue to investigate the mechanisms behind this ability to bounce back, which they’ve named anastasis. Apoptosis comes from Greek roots meaning “falling to death,” while anastasis means “rising to life.” Knowing more about anastasis could eventually lead to ways to enhance it, Montell says, which could be a boon for conditions in which apoptosis occurs to excess. On the other hand, identifying ways to reduce or prevent anastasis could help avert resistance to chemotherapy or other conditions where cell survival is harmful.

—Christen Brownlee

Reprinted with permission from the November issue of the Johns Hopkins Medicine Dome


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