On January 28, UCLA researchers announced the results of a study of heat shock proteins. Their findings may lead to new therapies for a variety of debilitating diseases. The results of their two-year study were published in the most recent issue of the journal Cell Stress and Chaperones, which is a peer-reviewed journal in the fields of cell stress response.
Heat shock proteins are a group of proteins the expression of which is increased when the cells are exposed to elevated temperatures. Their expression is increased when cells are exposed to taxing environmental conditions, such as infection, inflammation, exercise, exposure to toxins and other stressors. The findings by a group of researchers from the Jules Stein Eye Institute and UCLA Pulmonary and Critical Care Medicine run counter to conventional wisdom. They have discovered for the first time that a gene thought to express a protein in all cells that come under stress is instead expressed only in specific cell types. The investigators have focused on αB-Crystallin, which is a small heat shock protein. This protein may be associated with certain cancers and could be developed into a biomarker to monitor for diseases such as multiple sclerosis, age-related macular degeneration, heart muscle degeneration, and clouding of the eye lens. Any discoveries about how this protein is regulated and its molecular biology may reveal potential targets for new therapies for these conditions, noted study first author Zhe Jing, a research associate in UCLA Pulmonary and Critical Care Medicine. He explained, “If you use a certain cell type, this protein can be induced when the cells are stressed, but that doesn’t happen in a different cell type. This novel finding does conflict with what has been thought, that this protein could be induced in any cell type.”
The investigators conducted the study using four cell lines: two epithelial cells lines and two fibroblast cells lines. They found that the protein cannot be induced by stress in epithelial cells, in which 80% of cancers arise. However, it can be induced in the fibroblasts that make up muscle tissue. The significant finding in this research is that, in certain cell types, only one specific heat shock factor controls the expression of αB-Crystallin. For example, in the epithelial cell lines, it is heat shock factor 4 (HSF4), while a different heat shock factor, (HSF1), plays this role in the fibroblast cells lines. Past research has noted that a heat shock factor could control the expression of αB-Crystallin randomly and equally. However, Jing’s discovery overrides this rule. His findings strongly suggest the “preference” of the αB-Crystallin to heat shock factors in certain cells may be correlated with its versatility to various diseases. He explained, “Considering the multiple roles of αB-Crystallin in so many diseases, the access of the HSF1 and HSF4 to the αB-Crystallin gene dictated by the certain cell type may be what is helping to cause certain diseases. If we can uncover the cascade of events that result in disease, we may be able to come up with strategies to block or interrupt that cascade.”
The next step of this research is to validate what was found in this study by examining single cells. This provides a greater challenge; however, it may lead to further discoveries.