Factor Protects Cells From Fatty Acids

Researchers have identified a heart cell protein that responds to the presence of excess saturated fatty acids such as palmitate by initiating a sequence of steps that result in the death of the cell.

Investigators at Washington University School of Medicine (St. Louis, MO, USA) had previously worked with a transgenic mouse that accumulated fat in its heart muscle cells resulting in the death of the cells and subsequent heart failure. The cells of these animals contained levels of eEF1A-1 (eukaroytic elongation factor) nearly three-fold higher than those found in the hearts of normal animals.

To discover how eEF1A-1 was involved in fatty acid-induced cell death, the investigators genetically engineered CHO (Chinese hamster ovary) cell mutants resistant to palmitate-induced death, and isolated a clone with inactivated eEF1A-1. They reported in the February 2006 issue of Molecular Biology of the Cell that cells with disrupted eEF1A-1 expression were protected from palmitate lipotoxicity as well as being resistant to hydrogen peroxide- and endoplasmic reticulum (ER) stress-induced death. Lack of eEF1A-1 also resulted in disruption of the cells' actin cytoskeletons when they were exposed to palmitate. This finding suggested that the toxic effect of eEF1A-1 might be related to changes it causes in the cells' cytoskeletal structure.

"Cells have a lot of mechanisms for incorporating fatty acids into storage forms, for metabolizing them or for using them in cellular membranes,” said senior author Dr. Jean Schaffer, associate professor of medicine, molecular biology, and pharmacology at Washington University School of Medicine. "But saturated fats like palmitate are poorly stored in the tiny fat droplets normally found in most cells and therefore are more likely to enter into pathways that lead to cell death such as the one in which eEF1A-1 is involved.”