Proteins are key to cell death in heart disease, stroke and degenerative conditionsResearchers at Yale School of Medicine have gained deeper understanding of two members of a family of proteins called caspases that play a key role in promoting apoptosis, a process in which the cell responds to external signals by essentially committing suicide.
Published in the February 10 issue of Science, the study focused on caspase 3 and caspase 7. By breeding mice deficient in both of these proteins, the team was able to closely study their role in apoptosis, which is important to a wide range of normal physiologic processes, such as embryonic development and proper management of the immune system. Apoptosis also occurs in disease states, such as stroke, heart attacks and degenerative diseases such as Alzheimer's. Insufficient apoptosis can lead to autoimmune diseases and cancer.
In this study, mice that lacked caspases 3 and 7 had defects in cardiac development and died within the first day of life. "Using fibroblasts from these mice, we were able to determine that a lack of these two proteins renders individual cells highly resistant to dying," said first author on the study Saquib A. Lakhani, associate research scientist in the Department of Pediatrics and the Section of Immunobiology at Yale School of Medicine.
Lakhani and co-authors were further able to show that caspases 3 and 7 play a fundamental role in controlling mitochondrial events of apoptosis, including dissipation of energy production.
"Although mitochondria are primarily known as the energy generators of cells, they control apoptosis by releasing a variety of pro-apoptotic factors," said Lakhani. "These results provide further insight into the molecular control of apoptosis and are relevant to the wide variety of health and disease processes that rely on apoptosis."
Other authors on the study are Ali Masud, Keisuke Kuida, George A. Porter, Jr., Carmen J. Booth, Wajahat Z. Mehal, Irteza Inayat, and principal investigator Richard A. Flavell.
Citation: Science, Vol. 311, Issue 5762 (February 10, 2006)
Last reviewed: By John M. Grohol, Psy.D. on 30 Apr 2016
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