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The Dallas Morning News: Thursday | March 29, 2001 New research redefining knowledge of cell death Findings hold promise in treatment of cancer, brain conditions By Sue Goetinck Ambrose / The Dallas Morning News Scientists are breathing new life into death. It's not the kind of death that ends life. It's a natural form of suicide – by cells – that helps the body live. One new report suggests that when it comes to cell suicide, there is more than one way to die. If so, there may be fresh opportunities to treat devastating conditions such as Lou Gehrig's, Parkinson's and Huntington's diseases, all of which involve the death of brain cells. Other recent findings could help reduce the amount of chemotherapy needed to destroy cancer cells. Researchers may also have new clues about why cells can kill themselves at all. A recent study suggests that people and other animals inherited at least some of their suicide implements from lowly bacteria. In a typical day, researchers have estimated, more than 50 billion cells are born in the human body. And more than 50 billion cells kill themselves. Sometimes cells commit suicide if they receive a harmful dose of radiation – for instance, from too much sun exposure. That act of suicide is for the good of the body; it may prevent cancer or other problems caused by damaged cells. The immune system also depends on cell suicide to weed out unwanted immune cells, such as those that might attack healthy tissues. And death of cells is important in a budding life. Cell suicide is the reason people usually don't have webbed fingers and toes: Cells that connected the digits before birth have killed themselves. And a key step in a young brain's development is the loss of about half its cells through cell suicide. For years, scientists assumed that all these cells were dying the same way – through a process called apoptosis. During this kind of death, a cell actively destroys its own genetic material and then breaks into pieces easily digested by scavenger cells. But in a paper published recently in the Proceedings of the National Academy of Sciences, researchers proposed that cells kill themselves in another way. "This doesn't look anything like apoptosis," said Dale Bredesen of the Buck Institute for Age Research in Novato, Calif. "It's like night and day." In the new type of cell suicide – called paraptosis – cells appear to form large, fluid-filled puddles inside. That's never seen in apoptosis, Dr. Bredesen said. He and his colleagues also found that some of the telltale biochemical signs of apoptosis don't appear in paraptosis, suggesting that it's a different form of cell death. Dr. Bredesen noted that other researchers have found cases of cell death that don't look like apoptosis. Cells in mice with a form of Lou Gehrig's disease, for instance, also seem to develop puddles. So do cells in the developing nervous system, as well as the cells of some primitive life forms – a type of yeast and a slime mold. It could be that paraptosis is an ancient form of cell suicide that today is overshadowed by apoptosis. Dr. Bredesen's idea is controversial. "It still has to be proved or disproved," said Guy Salvesen, a biologist at The Burnham Institute in La Jolla, Calif. But if the idea holds up, Dr. Bredesen said, researchers may want to rethink their strategies for treating certain brain diseases. Dying brain cells from mice with a form of Huntington's disease don't have the hallmarks of apoptosis; neither do brain cells afflicted with Parkinson's, he said. And many biotechnology companies are trying to devise treatments for those diseases based on preventing apoptosis. But if paraptosis is the real culprit, those methods may not work, Dr. Bredesen said. Treatments for cancer may also get a boost from recent findings on cell suicide. Xiaodong Wang, a biochemist at the University of Texas Southwestern Medical Center at Dallas, has recently found a cell component called Smac that lifts barriers to apoptosis. Last year, Dr. Wang and his colleagues reported in the journal Nature that only a small fragment of Smac is needed to do the job. Because only a fragment is needed, it may be simpler to design drugs that can trigger apoptosis in certain situations. Cancer patients, for instance, could benefit from such drugs. Chemotherapy works by triggering apoptosis, and with the help of a drug that mimics Smac, milder doses of chemotherapy medicines might be given. Smac is released from compartments inside the cell called mitochondria. So is an enzyme that breaks down genetic material, another feature of apoptosis, Dr. Wang said. Mitochondria compartments help cells turn food into energy, and at first glance might not seem as if they should have anything to do with apoptosis. But Dr. Wang said there could be a connection. Many scientists believe that mitochondria are remnants of bacteria that began living as parasites inside another type of cell millions of years ago. Then the bacteria and the other cell developed a symbiotic relationship, the theory goes; eventually, the liaison gave rise to the cells that now form plants, fungi and animals – including people. But even today, Dr. Wang said, the mitochondria retain the ability to kill their host. Bacteria may have also made another donation that allows cells to kill themselves, research published this year in the journal Science suggests. A search through the human genetic blueprint hints that some of the genes that help human cells kill themselves are similar to genes in bacteria. It's possible, said Eugene Koonin of the National Center for Biotechnology Information, that this genetic gift occurred early in evolution but after bacteria invaded cells and became mitochondria. Life forms on Earth today probably would have been very different without those genetic donations, Dr. Koonin said. "If the tools for making this system had not been acquired," Dr. Koonin said, "there should have been some other way of coming up with doing the same thing." http://www.dallasnews.com/science/health/321261_apoptosis_26li.html ******** ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn