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姜黄素在 HepG2 细胞中发挥的细胞保护作用是通过 microRNA 介导的 BACH-1 和 HO-1 调节实现的。

Cytoprotective effect exerted by geraniin in HepG2 cells is through microRNA mediated regulation of BACH-1 and HO-1.

机构信息

Department of Zoology, Savitribai Phule Pune University, Pune - 411007, India.

AJ Organica Pvt. Ltd., Pune - 411007, India.

出版信息

BMB Rep. 2017 Nov;50(11):560-565. doi: 10.5483/bmbrep.2017.50.11.060.

DOI:10.5483/bmbrep.2017.50.11.060
PMID:28602161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5720469/
Abstract

Geraniin, a hydrolysable tannin, used in traditional medicine in Southeast Asia, is known to exhibit various biological activities. As an antioxidant it is known to up-regulate phase II enzyme Heme oxygenase-1 (HO-1). However its mechanism is not clearly understood. Nuclear factor erythroid-derived 2 related factor 2 (Nrf-2) is transcriptionally up-regulated by Extracellular signal-regulated kinase (ERK) 1/2 and retained in nucleus due to inactivated Glycogen synthase kinase 3 beta (GSK-3β). Geraniin additionally down-regulates expression of microRNA 217 and 377 (miR-217 and miR-377) which target HO-1 mRNA. Expression of BTB and CNC homolog 1 (BACH-1), another regulator of HO-1, is also down-regulated by up-regulating microRNA 98 (miR-98), a negative regulator of BACH-1. Thus, geraniin up-regulates HO-1 expression both through activating its positive regulator Nrf-2 and by down-regulating its negative regulator BACH-1. Up-regulation of HO-1 also confers protection to HepG2 cells from tertiary butyl hydroperoxide (TBH) induced cytotoxicity. [BMB Reports 2017; 50(11): 560-565].

摘要

没食子酸，一种可水解的单宁酸，在东南亚传统医学中被使用，已知具有多种生物活性。作为一种抗氧化剂，它可以上调Ⅱ相酶血红素加氧酶-1（HO-1）。然而，其机制尚不清楚。核因子红细胞衍生 2 相关因子 2（Nrf-2）通过细胞外信号调节激酶（ERK）1/2 转录上调，并由于糖基化酶激酶 3β（GSK-3β）失活而保留在核内。没食子酸还下调 microRNA 217 和 377（miR-217 和 miR-377）的表达，miR-217 和 miR-377 靶向 HO-1 mRNA。HO-1 的另一个调节剂 BTB 和 CNC 同源物 1（BACH-1）的表达也被 microRNA 98（miR-98）下调，miR-98 是 BACH-1 的负调节剂。因此，没食子酸通过激活其正调节剂 Nrf-2 并下调其负调节剂 BACH-1 来上调 HO-1 表达。HO-1 的上调也赋予 HepG2 细胞对叔丁基过氧化物（TBH）诱导的细胞毒性的保护作用。[BMB 报告 2017；50(11): 560-565]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/b6d59efa9bd3/bmb-50-560f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/8506cd35d504/bmb-50-560f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/642759924b10/bmb-50-560f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/5e30157bb6da/bmb-50-560f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/b6d59efa9bd3/bmb-50-560f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/8506cd35d504/bmb-50-560f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/642759924b10/bmb-50-560f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/5e30157bb6da/bmb-50-560f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da72/5720469/b6d59efa9bd3/bmb-50-560f4.jpg

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