Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase.

Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase.
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DOI:
10.5851/kosfa.2018.38.2.350
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发表时间:
2018-04
影响因子:
--
通讯作者:
Liong MT
Liong MT
中科院分区:
工程技术3区
文献类型:
--
作者:
Lew LC;Choi SB;Khoo BY;Sreenivasan S;Ong KL;Liong MT

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高胆固醇血症是心血管疾病的主要危险因素之一。使用乳酸菌益生菌来降低血液中的胆固醇水平已被广泛报道。然而,需要更多的信息来评估可能涉及的机制,并确定进一步治疗开发的可能靶点。在这项研究中,根据同化胆固醇的能力和防止胆固醇在肝脏(HepG2)和肠道(HT-29)细胞中积聚的能力来筛选乳杆菌菌株。与其他乳杆菌相比,植物乳杆菌DR7的无细胞培养上清(CFS)显示出更高的同化胆固醇的能力,减少了HepG2和HT-29细胞中胆固醇的积累,同时降低了HepG2中HMG-CoA还原酶(HMGCR)的mRNA表达(p<0.05)。在存在AMPK抑制剂(化合物C)的情况下,HMGCR表达的降低也被减弱,这表明植物乳杆菌DR7通过AMPK途径发挥作用,通常是通过AMPK的磷酸化而不是在HepG2中AMPK的mRNA表达(p<0.05)。综上所述,我们目前的研究表明,乳酸菌可以沿着AMPK途径发挥降胆固醇作用,特别是通过AMPK的磷酸化导致HMGCR表达减少。
Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.
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