Binding and detoxification ability of lactobacillus acidophilus towards di-n-butyl phthalate: Change of MAPK pathway in Caco-2 cell model

• Published in: Journal of proteomics Vol. 247; p. 104333
• Main Authors: Zhao, Lili, Xu, Mengfan, Pan, Xin, Zhang, Bolin, Dou, Qingnan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.09.2021
• Subjects: di-n-butyl phthalate; Lactobacillus acidophilus; MAPK; TNF; GADD45; PAT; JNK; Lactobacillus acidophilus; MTT; TNF; NF-κB; DMEM; di-n-butyl phthalate; DEGs; DBP; CREB; CASP3; HepG2; mTOR; KEGG; PAEs; HPLC; GO; FOS; MAPK; LAB; p21; DDIT3; RIN; DEPs; PUMA; OTA; ERK
• ISSN: 1874-3919
• DOI: 10.1016/j.jprot.2021.104333

Di-n-butyl phthalate (DBP), a common compound of phthalates, can pose a risk to humans as a contaminant in the food industry. At present, the molecular mechanism of gene and protein toxicity caused by DBP in human cells is unclear. This in vitro study investigated the potential of inactivated Lactobacillus acidophilus NCFM in alleviating the damage caused by DBP in Caco-2 cells. According to the results from transcriptome and proteome analyses, the Caco-2 cells treated by DBP was resulted finally endoplasmic reticulum stress and mitochondrial oxidative damage. The most important differentially expressed genes and proteins involved in Caco-2 cells treated with NCFM to relieve DBP's cytotoxicity were TNF, NF-κB, CREB, P21, GADD45, FOS and CASP3. The molecular mechanism of DBP toxicity alleviated by strain NCFM was involved the MAPK pathway, via DBP bind to strain NCFM and avoid the activation of TNF receptor by DBP, so down-regulated the NF-κB, CREB, P21, GADD45, and CASP3, relieving the apoptosis of Caco-2 cells. Overall, our data provide new insights into detoxification of phthalate by using Lactobacillus. Here we sequenced and assembled the transcriptome from Caco-2 cells which were treated with 4 groups: Control, DBP, strain NCFM, and strain NCFM+DBP groups, and combined it with proteome to characterize DBP detoxification genes/proteins through multiomics analysis. The cell viability in DBP treated groups were significantly increased by NCFM strain, indicating NCFM strain has the ability to alleviate the cytotoxicity of DBP via their binding ability with toxins. Furthermore, the results of transcriptome and proteome analysis showed that the signaling pathway of strain NCFM can alleviate DBP toxicity through MAPK pathway, and the potential biomarkers were identified too. This research may provided new information for developing new detoxification strategies for DBP. Intracellular biological responses and related proteins and genes involved in NCFM treatment to relieve DBP cytotoxicity. [Display omitted] •L. acidophilus NCFM strain can relieve DBP toxicity in Caco-2 cell line.•The tumor necrosis factor TNF activated by DBP was significantly reduced.•L. acidophilus NCFM can alleviate the mitochondrial damage through MAPK pathway.•NCFM strain can reduce the expression of Caspase proteins upregulated by DBP.•NCFM strain can diminish the cell cycle arrest and DNA damage in Caco-2 cell line.