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EMBARGOED FOR 5 PM PDT, JUNE 17, 1997
Reversing Shock: GENE PROTECTS AGAINST CELL DEATH
Shock can kill. A heart attack, stroke, infection or injury can cause the profound disturbance of normal cellular functioning that doctors call shock - a biochemical and metabolic catastrophe that can lead to cell death and even death of the entire organism.
University of Maryland School of Medicine researchers have found a potentially powerful new weapon for medicine's war on shock. Ironically, it's an oncogene implicated in a kind of cancer called B-cell lymphoma, from which it gets its name - bcl-2. The products of the bcl-2 gene help prevent cell death, which is a boon to a cancer cell, although ultimately harmful to its human host.
Now bcl-2 may prove helpful in preventing cell death caused by shock.
Dr. Benjamin F. Trump, professor and chairman of pathology at the medical school in Baltimore, and colleagues will present results of a study of bcl-2's protective effects, at the 20th Annual Conference on Shock, on June18 in Indian Wells, California.
"The precise mechanism by which bcl-2 inhibits cell death remains to be defined," said Trump, "but we believe that its protective action arises from its anti-oxidant properties, its interference with the cellular signaling process, and its modification of calcium ion transport within the cell."
Oxidants, which can damage cells, are released in enormous quantities by infection, inflammation and ischemia - a blockage of blood flow - making them a far greater threat than one might think, the pathologist pointed out.
For more than a decade, Trump's research has focused on the role played by ionized or electrically charged calcium, which can increase rapidly within cells after they are damaged, activating biochemical and metabolic changes that can lead to cell death.
Dr. Masato Ichimiya, a surgeon and research fellow in Trump's lab, and Dr. Paul Amstad, associate professor of pathology at the University of Maryland School of Medicine, engineered normal cells from rats' kidneys to express extra bcl-2. Those cells proved more resistant than normal controls to death from treatment with hydrogen peroxide. The toxicity of hydrogen peroxide was further reduced by pretreating cells with a chemical that binds calcium ions.
After treatment with another chemical that releases calcium ions, the amount of positively charged intracellular calcium increased in both bcl-2 cells and controls, but calcium levels in cells containing bcl-2 dropped again much more rapidly.
Trump said his lab's findings suggest that bcl-2 protects against two kinds of cell death, apoptosis and oncosis. In apoptosis, most frequently seen in normal or "programmed" cell death, a cell shrinks, breaks into fragments and is absorbed by other housecleaning cells known as phagocytes. Oncosis, in which a cell swells and bursts, is more typical of cell death from shock following traumatic injury, infection or ischemia. "Cells overexpressing bcl-2 may prevent oxidant-induced cell death in part by increasing the cells' ability to effectively buffer the effects of increased calcium ions," Trump and Ichimiya concluded. "This could be significant in developing effective methods of preventing and treating shock, which is a major cause of death."
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