severe metabolic stress and can push some cells in the body to commit suicide. These cells don't have the ability to tolerate the toxic environment excess fat and sugar cause, and ultimately initiate their own death.
St. Louis have recently discovered three unexpected culprits that help
a cell overloaded with fat commit suicide. They've demonstrated that
these molecules leading a cell to self-destruct are small strands of RNA,
not proteins. Since these small nuclear RNAs play well-known roles
in building proteins, the researchers were surprised to discover them
to link these small RNA molecules to the cellular damage characteristic
of common metabolic diseases like diabetes.
metabolic stress, such as exposure to large amounts of fats," says cardiologist Jean E. Schaffer, MD, the Virginia Minnich Distinguished Professor of Medicine at Washington University. "But if these three
RNAs are missing, the cells don't die."
gets shut down, damaged cells may
divide and lead to cancer.
diabetes complications such as heart failure. It is important to
understand how abnormal metabolites cause cells to die, it will be
helpful in the search for effective new therapies.
Center at the School of Medicine, the fact that small RNA molecules
are involved in this cell death pathway is totally unexpected.
fat, we were expecting to find genes that code for proteins," she explains. "Instead, we identified an entirely new function for three small nuclear RNAs. Unrelated to their well-defined role in the cell's protein-making machinery, we discovered they participate in how cells go on to die
from overload of nutrients."
fat and high sugar conditions. While the region codes for a protein, they demonstrated that the protein itself is not involved in initiating cell death.
mutation occurs in a region that encodes a protein, as we might expect.
But returning the protein to the mutated cells did not return the cell death response."
The three small nuclear RNAs function together not only to promote
cell death from nutrient excess, but also to promote more general mechanisms of cell death in diseased tissues.
the complexities of metabolic diseases like diabetes and obesity. Encouraging patients to reduce the amount of fat and sugar in the diet
is a key strategy for treatment.
have other ways to reduce cellular damage from excess fats in the
muscles, heart, pancreas, liver and other organs and the team continues
to pursue the search for possible treatments. "That's where our future
work is headed."
Health (NIH), the Burroughs Wellcome Foundation, the Washington University Diabetes Research Training Center and the Washington University Metabolomics facility.
are critical mediators of metabolic stress. Cell Metabolism, July 2011