Premium
Gene transfer of the Caenorhabditis elegans n‐3 fatty acid desaturase inhibits neuronal apoptosis
Author(s) -
Ge Yinlin,
Wang Xiaoying,
Chen Zhihong,
Landman Natalie,
Lo Eng H.,
Kang Jing X.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01077.x
Subject(s) - caenorhabditis elegans , polyunsaturated fatty acid , biology , apoptosis , fatty acid desaturase , fatty acid , gene expression , stearoyl coa desaturase , programmed cell death , eicosanoid , arachidonic acid , microbiology and biotechnology , gene , prostaglandin , biochemistry , enzyme
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 E 2 , 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.