According to researchers from John Hopkins, a new insight has been developed pertaining to the target and action of cholesterol-reducing drugs on a daily basis by millions of patients to stave off ailments such as strokes and heart attacks.

It was found that a yeast known as fission yeast proves to be an effective model for delving quick and deep into the molecular details of how mammalian cells tend to regulate HMG-CoA reductase.

The findings were seen as a surprising fundamental difference by Peter J. Espenshade, a physiologist in the Department of Cell Biology and member of the Center for Metabolism and Obesity Research at the Johns Hopkins University School of Medicine.

From News-Medical.Net:

The Johns Hopkins team’s seek-and-find mission for new parts of the molecular machine that regulates the manufacture of cholesterol builds on Nobel-prize winning research by Michael S. Brown and Joseph L. Goldstein of the Department of Molecular Genetics, University of Texas - Southwestern Medical School, who discovered that cells of the human body have receptors on their surfaces that trap and absorb bloodstream particles containing cholesterol.

Using fission yeast, the Johns Hopkins scientists identified the protein Insig as an integral part of the sensor system in cells that measures cholesterol levels. When all is well with cells, they happily go about their business of manufacturing cholesterol in just the right amounts, as determined by their Insig-regulated sensors, Espenshade says.

As in humans, Insig in yeast limits cholesterol production by inactivating the enzyme HMG-CoA reductase. How the yeast stopped synthesizing cholesterol was what surprised the scientists, however.

Stressed fission yeast activated a protein called MAPK which, partnering with the protein Insig, attaches a phosphate onto the enzyme HMG-CoA reductase by a process known as phosphorylation and shuts down cholesterol manufacture. These findings explain how a cell can change cholesterol production in response to a stressful environment.

It is expected that after these findings, researchers are hoping to communicate the new improvements to efficacies of other cholesterol-lowering therapies and statin.

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Tags: cholesterol production, cholesterol-reducing drugs, fission yeast, mammalian cells, MAPK

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