Arachidonic acid regulates unsaturated fatty acid synthesis in lymphocytes by inhibiting stearoyl-CoA desaturase gene expression.
This work was based upon the observation that a reduction in the level of serum, provided to murine lymphocytes in culture, augmented endogenous unsaturated fatty acid (UFA) synthesis. Since the phospholipids of BW5147 cells grown in 1% serum were especially deficient in arachidonic acid (20:4), and given the findings of previous workers, we suspected that the availability of exogenous 20:4 in serum might correlate with the squelching of UFA synthesis. Indeed, after a 5 h exposure to 4-28 microM 20:4, the 20:4 content of BW5147 cell phospholipids increased from 1% to 15% of the total fatty acids with a coincident reduction in 18:1 synthesis to approx. 30% of starting values. Subsequent studies were done to define the mechanism by which 20:4 down-regulates 18:1 synthesis. The results indicated that 20:4 inhibited endogenous 18:1 synthesis by reducing stearoyl-CoA desaturase (SCD) enzyme activity. Moreover, as determined by Northern blot analyses, the inhibitory effect of 20:4 on stearoyl-CoA desaturase activity coincided with decreased stearoyl-CoA desaturase mRNA levels. Exposure of BW5147 cells to either 20:4, actinomycin D, or both, resulted in a temporal decay of stearoyl-CoA desaturase mRNAs with half-lives ranging from 4.0 h to 4.4 h. Such a similarity in decay times implied that 20:4 regulates stearoyl-CoA desaturase expression by inhibiting transcription. This was confirmed by nuclear run-on studies in which 20:4 was found to inhibit transcription of nascent stearoyl-CoA desaturase mRNA. Collectively, these findings implicate 20:4 as an important regulator of stearoyl-CoA desaturase gene expression, and hence UFA synthesis, in lymphoid cells.
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858-4354.
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PW
Tebbey
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Buttke
D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D015152:Blotting, Northern; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger; D016718:Arachidonic Acid; D013230:Stearoyl-CoA Desaturase