Cell Killer

Scientists have found a chemical that 

makes cells commit suicide, reports Biplab Das 

Suicide is not always a tragedy. Sometimes it is the best way to get rid of a miscreant, especially when it is something like a cell infected with a fatal microbe. Some scientists in Calcutta have discovered ways to force damaged cells commit mass suicide. "We've found a molecule called ceramide, which plays pivotal role in mass hara-kiri or apoptosis of an infected cell," says Subrata Majumder, a cell biologist at the Bose Institute. 

In a paper to be published, Majumder and his team, comprising research students Sanjukta Ghosh and Sonali Das, claim to have found out how ceramide ushers in death in human neutrophils (a type of white blood cell). The study has roots in a previous work in which they came across a group of curious proteins called tumour necrosis factor (TNF) alpha. This protein can stifle a growing tumour in the body.

In fact, TNF alpha induces ceramide production inside the cells. To find out how TNF gets involved in ceramide production, the research team grew human neutrophils in a laboratory dish and exposed them to a microbe. In general, neutrophils along with other members (T cells, B cells) of our defence system rush to the site of microbes' invasion and battle out the trespassers. But when innumerable microbes invade the cells, a large number of immune cells are called into action. In such a crisis, activated neutrophils release a substance called cytokine that plays an important role in the regulation of immune system. The cytokine in turn gets attached to certain receptors on the cell membrane. Now, this cytokine's message via receptor activates the enzyme, sphingmyclinase (Smase) inside the cells. At this point, Majumder's team found that activated Smase synthesizes ceramide to drive cells towards cell death. 

After this, Majumder's team undertook an experiment in a group of albino (white) mice. Certain protective cells of the lab mice were infected with the germs of Kala-azar (Leishmania donovani). Infected cultured macrophages showed up higher concentration of ceramide compared to controls. 

Ceramide, at higher concentration, activates a protein, which, in turn, modulates inflammation and infection. According to Majumder's group, a higher concentration of ceramide could drive the cells to follow sudden death or necrosis initiating chronic infection. "We now plan to develop something similar to ceramide. If added from outside, it may help regulate ceramide concentration inside the cells," says Majumder. "This would direct cells to follow the path of suicide (apoptosis) rather than a path of sudden death (necrosis)." 

Other research groups also found that ceramide triggers the release of another protein - cytochrome C - which causes apoptosis. Inducing ceramide-mediated apoptosis, researchers could stop the uncontrolled proliferation of cells in cancer. Moreover, in a recent research, ceramide has been reported to have some implications in cellular death in AIDS. It is also said to be mediating natural cell death in aging. But, right now, Majumder's team aims to carry on their research for a deeper insight into the ceramide-mediated death zone and find out a better way to exploit ceramide for several dreaded diseases.