Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis |
| |
Authors: | Ge Yinlin Wang Xiaoying Chen Zhihong Landman Natalie Lo Eng H Kang Jing X |
| |
Institution: | Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. |
| |
Abstract: | Previous studies have shown that n-3 polyunsaturated fatty acids (PUFAs) can exert an antiapoptotic effect on neurons. The present study was designed to investigate whether the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase (an enzyme that converts n-6 PUFAs to corresponding n-3 PUFAs) can be expressed functionally in rat cortical neurons and whether its expression can change the ratio of n-6 : n-3 fatty acids in the cell membrane and exert an effect on neuronal apoptosis. Infection of primary rat cortical cultures with Ad-fat-1 resulted in high expression of the fat-1 gene. Lipid analysis indicated a decrease in the ratio of n-6 : n-3 PUFAs from 5.9 : 1 in control cells, to 1.45 : 1 in cells expressing the n-3 fatty acid desaturase. Accordingly, the levels of prostaglandin E2, an eicosanoid derived from n-6 PUFA, were significantly lower in cells infected with Ad-fat-1 when compared with control cells. Finally, there was a significant inhibition of growth factor withdrawal-induced apoptotic cell death in neurons expressing the fat-1 gene. These results demonstrate that expression of the fat-1 gene can inhibit apoptotic cell death in neurons and suggest that the change in the n-6 : n-3 fatty acid ratio may play a key role in this protective effect. |
| |
Keywords: | apoptosis fat‐1 n‐3 fatty acids n‐6 fatty acids neurons polyunsaturated fatty acids |
本文献已被 PubMed 等数据库收录! |
|