Abstract
Astrocytes play a vital role in brain lipid metabolism; however the impact of the phenotypic shift in astrocytes to a reactive state on arachidonic acid metabolism is unknown. Therefore, we determined the impact of dibutyryl-cAMP (dBcAMP) treatment on radiolabeled arachidonic acid ([1-14C]20:4n-6) and palmitic acid ([1-14C]16:0) uptake and metabolism in primary cultured murine cortical astrocytes. In dBcAMP treated astrocytes, total [1-14C]20:4n-6 uptake was increased 1.9-fold compared to control, while total [1-14C]16:0 uptake was unaffected. Gene expression of long-chain acyl-CoA synthetases (Acsl), acyl-CoA hydrolase (Acot7), fatty acid binding protein(s) (Fabp) and alpha-synuclein (Snca) were determined using qRT-PCR. dBcAMP treatment increased expression of Acsl3 (4.8-fold) and Acsl4 (1.3-fold), which preferentially use [1-14C]20:4n-6 and are highly expressed in astrocytes, consistent with the increase in [1-14C]20:4n-6 uptake. However, expression of Fabp5 and Fabp7 were significantly reduced by 25% and 45%, respectively. Acot7 (20%) was also reduced, suggesting dBcAMP treatment favors acyl-CoA formation. dBcAMP treatment enhanced [1-14C]20:4n-6 (2.2-fold) and [1-14C]16:0 (1.6-fold) esterification into total phospholipids, but the greater esterification of [1-14C]20:4n-6 is consistent with the observed uptake through increased Acsl, but not Fabp expression. Although total [1-14C]16:0 uptake was not affected, there was a dramatic decrease in [1-14C]16:0 in the free fatty acid pool as esterification into the phospholipid pool was increased, which is consistent with the increase in Acsl3 and Acsl4 expression. In summary, our data demonstrates that dBcAMP treatment increases [1-14C]20:4n-6 uptake in astrocytes and this increase appears to be due to increased expression of Acsl3 and Acsl4 coupled with a reduction in Acot7 expression.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Prostaglandins, Leukotrienes and Essential Fatty Acids
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.