Nara Takayuki Y, He Wei Song, Tang Chongren, Clarke Steven D, Nakamura Manabu T
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA.
Biochem Biophys Res Commun. 2002 Aug 9;296(1):111-7. doi: 10.1016/s0006-291x(02)00851-3.
Delta-6 Desaturase (D6D) catalyzes the first step of the synthesis of highly unsaturated fatty acids (HUFA) that play pivotal roles in many biological functions. The D6D expression is under feedback regulation by dietary HUFA. We co-transfected D6D promoter-reporter constructs to HepG2 cells with an expression vector of nuclear form sterol regulatory element binding protein-1c (SREBP-1c). A 90-bp region of the D6D promoter was required for the activation by SREBP-1c as well as for the suppression of the promoter activity by HUFA. The region contained two candidates of sterol regulatory element (SRE). Mutation analysis identified E-box like SRE (SRE-2) as essential for both SREBP-1c activation and HUFA suppression. SRE-2 has a core sequence of CAGCAG, and is also conserved in stearoyl CoA desatruases. Because HUFA are primarily incorporated into phospholipids (PL), our results suggest that the primary role of SREBP-1c in liver is the regulation of fatty acid supply for PL rather than for triglycerides.
Δ-6去饱和酶（D6D）催化高不饱和脂肪酸（HUFA）合成的第一步，而高不饱和脂肪酸在许多生物学功能中起着关键作用。D6D的表达受膳食HUFA的反馈调节。我们将D6D启动子-报告基因构建体与核形式固醇调节元件结合蛋白-1c（SREBP-1c）的表达载体共转染至HepG2细胞。D6D启动子的一个90bp区域对于SREBP-1c的激活以及HUFA对启动子活性的抑制都是必需的。该区域包含两个固醇调节元件（SRE）候选序列。突变分析确定类E盒SRE（SRE-2）对于SREBP-1c激活和HUFA抑制均至关重要。SRE-2具有CAGCAG核心序列，并且在硬脂酰辅酶A去饱和酶中也保守。由于HUFA主要掺入磷脂（PL）中，我们的结果表明SREBP-1c在肝脏中的主要作用是调节用于PL而非甘油三酯的脂肪酸供应。
