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. 2011 Feb;1811(2):111-7.
doi: 10.1016/j.bbalip.2010.10.005. Epub 2010 Nov 9.

Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain

Hyung-Wook Kim  1 , Jagadeesh S Rao, Stanley I Rapoport, Miki Igarashi
Affiliations

Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain

Hyung-Wook Kim et al. Biochim Biophys Acta. 2011 Feb.

Abstract

Background: Dietary n-3 polyunsaturated fatty acid (PUFA) deprivation increases expression of arachidonic acid (AA 20:4n-6)-selective cytosolic phospholipase A(2) (cPLA(2)) IVA and cyclooxygenase (COX)-2 in rat brain, while decreasing expression of docosahexaenoic acid (DHA 22:6n-3)-selective calcium-independent iPLA(2) VIA. Assuming that these enzyme changes represent brain homeostatic responses to deprivation, we hypothesized that dietary n-6 PUFA deprivation would produce changes in the opposite directions.

Methods: Brain expression of PUFA-metabolizing enzymes and their transcription factors was quantified in male rats fed an n-6 PUFA adequate or deficient diet for 15weeks post-weaning.

Results: The deficient compared with adequate diet increased brain mRNA, protein and activity of iPLA(2) VIA and 15-lipoxygenase (LOX), but decreased cPLA(2) IVA and COX-2 expression. The brain protein level of the iPLA(2) transcription factor SREBP-1 was elevated, while protein levels were decreased for AP-2α and NF-κB p65, cPLA(2) and COX-2 transcription factors, respectively.

Conclusions: With dietary n-6 PUFA deprivation, rat brain PUFA metabolizing enzymes and some of their transcription factors change in a way that would homeostatically dampen reductions in brain n-6 PUFA concentrations and metabolism, while n-3 PUFA metabolizing enzyme expression is increased. The changes correspond to reported in vitro enzyme selectivities for AA compared with DHA.

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Figures

Figure 1
Figure 1. Expression of brain PLA2 enzymes with n-6 PUFA deprivation
mRNA, protein levels and activities of iPLA2 (A-C), cPLA2 (D-F) and sPLA2 (G-I). mRNA data are expressed as the relative level of the PLA2 normalized to the endogenous control (β-globulin) using the ΔΔCT method. Protein levels are ratios of optical density of PLA2 to β–actin, expressed as percent of control. Values are mean ± SD (n = 10 for both groups). *p < 0.05, **p < 0.01. A, adequate; D, deficient.
Figure 2
Figure 2. Expression of brain transcription factors
Protein levels of SREBP-1, SREBP-2, AP-2α, AP-2β, NF-κB p65 and NF-κB p50 (A to F in order). Lamin B antibody was used as the nuclear protein control. The protein level is the ratio of optical density of transcription factor to β–actin, expressed as percent of control. Values are mean ± SD (n = 10 for both groups). *p < 0.05, **p < 0.01. A, adequate; D, deficient.
Figure 2
Figure 2. Expression of brain transcription factors
Protein levels of SREBP-1, SREBP-2, AP-2α, AP-2β, NF-κB p65 and NF-κB p50 (A to F in order). Lamin B antibody was used as the nuclear protein control. The protein level is the ratio of optical density of transcription factor to β–actin, expressed as percent of control. Values are mean ± SD (n = 10 for both groups). *p < 0.05, **p < 0.01. A, adequate; D, deficient.
Figure 3
Figure 3. Brain expression of cyclooxygenases
mRNA and protein levels of COX-2 (A and B) and COX-1 (C and D). mRNA data are expressed as relative level of PLA2 normalized to endogenous control (β-globulin) using the ΔΔCT method. The protein level is ratio of optical density of COX to β–actin, expressed as percent of control. Values are mean ± SD (n = 10 for both groups). *p < 0.05. A, adequate; D, deficient.
Figure 4
Figure 4. Brain expression of lipoxygenases
mRNA and protein levels of 5-LOX (A and D), 12-LOX (B and E) and 15-LOX (C and F). mRNA data are expressed as the relative level of PLA2 normalized to the endogenous control (β-globulin) using the ΔΔCT method. Protein level is ratio of optical density of PLA2 to β–actin, expressed as percent of control. Values are mean ± SD (n = 10 for both groups). *p < 0.05. A, adequate; D, deficient.
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