Sen and colleagues had linked TCT's effects to various substances that are activated in the brain after a stroke before they concluded that this enzyme could serve as an important therapeutic target. The enzyme is called cystolic calcium-dependent phospholipase A2, or cPLA2.
Following the trauma of blocked blood flow associated with a stroke, an excessive amount of glutamate is released in the brain. Glutamate is a neurotransmitter that, in tiny amounts, has important roles in learning and memory. Too much of it triggers a sequence of reactions that lead to the death of brain cells, or neurons the most damaging effects of a stroke.
Sen and colleagues used cells from the hippocampus region of developing mouse brains for the study. They introduced excess glutamate to the cells to mimic the brain's environment after a stroke.
With that extra glutamate present, the cPLA2 enzyme releases a fatty acid called arachidonic acid into the brain. Under normal conditions, this fatty acid is housed within lipids that help maintain cell membrane stability.
But when it is free-roaming, arachidonic acid undergoes an enzymatic chemical reaction that makes it toxic the final step before brain cells are poisoned in this environment and start to die. Activation of the cPLA2 enzyme is required to release the damaging fatty acid in response to insult caused by high levels of glutamate.
Sen and colleagues introduced the tocotrienol vitamin E to the cells that had already been exposed to excess glutamate. The presence of the vitamin decreased the release of fatty acids by 60 percent when compared to cells exposed to glutamate alone.
Brain cells exposed to excess glutamate followed by tocot
|Contact: Chandan Sen|
Ohio State University