Gene and protein expression profiling of the fat-1 mouse brain.
Polyunsaturated fatty acids (PUFAs) are essential structural components of all cell membranes and, more so, of the central nervous system. Several studies revealed that n-3 PUFAs possess anti-inflammatory actions and are useful in the treatment of dyslipidemia. These actions explain the beneficial actions of n-3 PUFAs in the management of cardiovascular diseases, inflammatory conditions, neuronal dysfunction, and cancer. But, the exact molecular targets of these beneficial actions of n-3 PUFAs are not known. Mice engineered to carry a fat-1 gene from Caenorhabditis elegans add a double bond into an unsaturated fatty acid hydrocarbon chain and convert n-6 to n-3 fatty acids. This results in an abundance of n-3 eicosapentaenoic acid and docosapentaenoic acid specifically in the brain and a reduction in n-6 fatty acids of these mice that can be used to evaluate the actions of n-3 PUFAs. Gene expression profile, RT-PCR and protein microarray studies in the hippocampus and whole brain of wild-type and fat-1 transgenic mice revealed that genes and proteins concerned with inflammation, apoptosis, neurotransmission, and neuronal growth and synapse formation are specifically modulated in fat-1 mice. These results may explain as to why n-3 PUFAs are of benefit in the prevention and treatment of diseases such as Alzheimer's disease, schizophrenia and other diseases associated with neuronal dysfunction, low-grade systemic inflammatory conditions, and bronchial asthma. Based on these data, it is evident that n-3 PUFAs act to modulate specific genes and formation of their protein products and thus, bring about their various beneficial actions.
Ménesi
Dalma
D
Functional Genomics Laboratory, Biological Research Center of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary.
Kitajka
Klára
K
Molnár
Eszter
E
Kis
Zoltán
Z
Belleger
Jérome
J
Narce
Michael
M
Kang
Jing X
JX
Puskás
László G
LG
Das
Undurti N
UN
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D040081:Protein Array Analysis
D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases