Title：Lactobacillus fermentum Postbiotic-induced Autophagy as Potential Approach for Treatment of Acetaminophen Hepatotoxicity

标题：乳酸发酵菌 Postbiotic 诱导的自噬可能是治疗对乙酰氨基酚肝毒性的潜在方法

作者:Miroslav Dinić, Jovanka Lukić, Jelena Đokić, Marina Milenković, Ivana Strahinić, Nataša Golić, Jelena Begović

发表期刊:Frontiers in Microbiology, 2017, 8: 594.

DOI:10.3389/fmicb.2017.00594

Abstract：

The aim of this study was to investigate the potential of postbiotics originated from Lactobacillus fermentum BGHV110 strain (HV110) to counteract acetaminophen (APAP)-induced hepatotoxicity in HepG2 cells. This strain was selected according to its autophagy inducing potential, based on previous studies reporting protective role of autophagy in APAP caused cellular damage. Cell viability was assessed using MTT and LDH assays, while autophagy was monitored by qPCR analysis of BECN1, Atg5, p62/SQSTM1, and PINK1 mRNA expression and by Western blot analysis of p62/SQSTM1 and lipidated LC3 accumulation. Our results showed that detrimental effect of APAP on cell viability was suppressed in the presence of HV110 which was linked with increased conversion of LC3 protein and p62/SQSTM1 protein degradation. Additionally, higher p62/SQSTM1 and PINK1 mRNA transcription were noticed in cells co-treated with APAP/HV110, simultaneously. In conclusion, this study suggests that HV110 enhances activation of PINK1-dependent autophagy in HepG2 cells and its eventual co-supplementation with APAP could be potentially used for alleviation of hepatotoxic side effects caused by APAP overdose.

摘要：

该研究旨在探讨源自Lactobacillus fermentum BGHV110菌株的后生物对扑热息痛（APAP）引起的肝毒性的潜在对抗作用。选择该菌株是基于其诱导自噬的潜力，之前的研究报告了自噬在APAP引起的细胞损伤中的保护作用。通过MTT和LDH测定法评估细胞活力，同时通过qPCR分析BECN1、Atg5、p62/SQSTM1和PINK1 mRNA表达以及Western blot分析p62/SQSTM1和脂化LC3积累来监测自噬。结果显示，在HV110存在的情况下，APAP对细胞活力的有害影响被抑制，这与LC3蛋白的转化和p62/SQSTM1蛋白降解的增加有关。此外，在APAP/HV110共同处理的细胞中，p62/SQSTM1和PINK1 mRNA转录增加。综上所述，该研究表明HV110增强了HepG2细胞中PINK1依赖的自噬激活，其与APAP的共同补充可能用于减轻APAP过量引起的肝毒性副作用。

Key Compounds and their CAS Numbers (主要化合物及其CAS号)

Acetaminophen (扑热息痛, APAP): 103-90-2

p62/SQSTM1: 不作为纯化学物质存在，通常作为抗体产品

LC3 (Microtubule-associated proteins 1A/1B light chain 3): 不作为纯化学物质存在，通常作为抗体产品

BECN1 (Beclin 1): 不作为纯化学物质存在，通常作为抗体产品

PINK1 (PTEN-induced putative kinase 1): 不作为纯化学物质存在，通常作为抗体产品