Summary of Study ST002877

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001799. The data can be accessed directly via it's Project DOI: 10.21228/M85M79 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002877
Study TitleMetabolic Profiling of Raw264.7 Mouse Macrophage Cells Cultured with Alanine
Study SummaryTo identify the catabolites of L-Alanine on promoting phagocytosis, GC-MS based metabolomics analysis was adopted to explore L-Alanine-reprogrammed metabolome. The metabolic flow of the TCA cycle was dysregulated. Meanwhile, six metabolites (oleate, palmitate, stearate, myristate, arachidonate and linoleate) in biosynthesis of saturated and unsaturated fatty acids were increased upon L-Alanine treatment, where palmitate was the biggest absolute increment in abundance. Thus, L-Alanine promotes the biosynthesis of fatty acids.
Institute
Sun Yat-sen University
Last Namejiang
First Nameming
AddressNo. 135, Xingang Xi Road, Guangzhou, 510275, P. R. China, guangzhou, guangdong, 510006, China
Emailjiangm28@mail.sysu.edu.cn
Phone13434283781
Submit Date2023-09-14
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailGC-MS
Release Date2023-09-26
Release Version1
ming jiang ming jiang
https://dx.doi.org/10.21228/M85M79
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001799
Project DOI:doi: 10.21228/M85M79
Project Title:Exogenous L-Alanine promotes phagocytosis via dual regulations of TLR4 to eliminate multidrug-resistant bacterial pathogens
Project Type:MS quantitative analysis
Project Summary:Multidrug-resistant bacteria present a major threat to public health. Therefore, new drugs or approaches are urgently needed to manage and mitigate this threat. Here, we screen the molecular candidates that allow the survival of mice upon multidrug-resistant Vibrio parahaemolyticus infection by integrated proteomic and metabolomics analysis, where L-Alanine metabolism and phagocytosis are highly correlated. The role of L-Alanine on boosting mouse survival is further confirmed with in vivo bacterial challenge studies on multidrug-resistant bacteria including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae. Functional studies demonstrate that exogenous L-Alanine promotes phagocytosis to these different species of multidrug-resistant pathogens. The underlying mechanism involves two events that are L-Alanine-dependently increased TLR4 expression, and L-Alanine-enhanced TLR4 signaling via increasing the biosynthesis and secretion of fatty acids such as palmitate. Palmitate enhances the binding of LPS to TLR4 and thereby promotes TLR4 dimmer formation and endocytosis for the subsequent activation of PI3K/Akt and NF-κB pathways and phagocytosis of bacteria. These results suggest that modulation of metabolic environment is a plausible approach for combating infection with multidrug-resistant bacteria.
Institute:sun yat-sen university
Last Name:jiang
First Name:ming
Address:No. 135, Xingang Xi Road, Guangzhou, 510275, P. R. China, guangzhou, guangdong, 510006, China
Email:jiangm28@mail.sysu.edu.cn
Phone:13434283781
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