Kazlauskas and his team were determined to answer those questions. To do so they created laboratory conditions that would allow them to observe the two enzymes separately as they acted on the lipid. In a series of "in vitro" or laboratory experiments that controlled the presence of each enzyme, they began to understand the individual roles of those enzymes.
The research team discovered the following. When the PI3K enzyme acts on the lipid, it converts it (the lipid) into a modified form of itself, which then signals blood vessel cells to proliferate or grow. The team also found that when PLCg acts on the lipid, it cuts the lipid in two, thus preventing PI3K from using that very same lipid to promote vessel growth. Instead, they learned, the resulting two halves of the lipid trigger a series of signaling activities that caused vessels to regress and disappear.
The team concluded that it was the competitive relationship between these two enzymes for the lipid that was at least part of the intracellular switch for which they and other scientists have been searching. They also concluded that blood vessel growth or regression was dependent on the relative activity of the two enzymes and on the amount of the lipid within the endothelial cells.
"Understanding this process opens a whole new avenue for treatment of angiogenesis-related diseases," says Kazlauskas. "For instance, drugs could be designed to decrease PI3K in cancer patients or those with proliferative diabetic retinopathy or macular degeneration, or designed to increased it in a d
Source:Harvard Medical School