Researchers have demonstrated that HIV protease inhibitors block a cellular enzyme important for generating the structural scaffolding for the cell nucleus.
Scientists from the University of California, Los Angeles and Purdue University started by adding HIV protease inhibitors to cultures of mouse and human fibroblast cells. They found that the inhibition of ZMPSTE24 by HIV protease inhibitor drugs led to an accumulation of prelamin A, which is a precursor to mature lamin A. ZMPSTE24 is required for the normal conversion of prelamin A to mature lamin A. The team observed that the accumulation of prelamin A was exaggerated in cells that contained half the normal amount of ZMPSTE24.
These biochemical findings, according to the investigators, may offer insights into the side effects of HIV protease inhibitors, including metabolic syndrome and regional losses of some of the body’s fat tissue, which have also been caused by genetic defects in ZMPSTE24.
The study was published in the July 16 early edition of Proceedings of the National Academy of Sciences.