Summary of Study ST003030

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 PR001883. The data can be accessed directly via it's Project DOI: 10.21228/M89X4H This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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 ID	ST003030
Study Title	A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation - Part 2
Study Summary	Macrophage migration inhibitory factor (MIF) is an innate cytokine that regulates both inflammatory and homeostatic responses. MIF is expressed by cardiomyocytes, where it exerts a protective action against ischemia-reperfusion (I/R) injury by activating AMP-activated protein kinase (AMPK). This effect is attenuated in the senescent heart due to an intrinsic, age-related reduction in MIF expression. We hypothesized that treating the aged heart with the small molecule MIF agonist (MIF20) can reinforce protective MIF signaling in cardiomyocytes, leading to a beneficial effect against I/R stress. The administration of MIF20 at the onset of reperfusion was found to not only decrease myocardial infarct size but also preserves systolic function in the aged heart. Protection from I/R injury was reduced in mice with cardiomyocyte-specific Mif deletion, consistent with the mechanism of action of MIF20 to allosterically increase MIF affinity for its cognate receptor CD74. We further found MIF20 to contribute to the maintenance of mitochondrial fitness and to preserve the contractile properties of aged cardiomyocytes under hypoxia/reoxygenation. MIF20 augments protective metabolic responses by reducing the NADH/NAD ratio, leading to a decrease in the accumulation of reactive oxygen species (ROS) in the aged myocardium under I/R stress. We also identify alterations in the expression levels of the downstream effectors PDK4 and LCAD, which participate in the remodeling of the cardiac metabolic profile. Data from this study demonstrates that pharmacologic augmentation of MIF signaling provides beneficial homeostatic actions on senescent myocardium under I/R stress.
Institute	University of Mississippi Medical Center
Last Name	Li
First Name	Ji
Address	2500 N State St, Jackson, MS 39216-4505
Email	jli3@umc.edu
Phone	6018158995
Submit Date	2023-12-18
Analysis Type Detail	LC-MS
Release Date	2024-06-18
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP003150
Sampleprep Summary:	The metabolomic sample preparation method was: The tissue samples were ground into a homogenous powder with a Retsch Cryomill (Retsch-Allee, Haan, Germany). 45 – 80 mg of the pulverized sample was weighed and stored in the -80 oC freezer prior to extraction. Samples were allowed to thaw at 4 °C for 30 min before adding 1.5 mL of 20:40:40 water/methanol/acetonitrile with 0.1 M formic acid for metabolites extraction. The samples were vortexed and centrifuged and the supernatants were isolated and dried completely under nitrogen. The dried samples were resuspended in 300 µL water and an aliquot were transferred to autosampler vials for UHPLC-HRMS analysis. Mass analysis was carried out at the University of Tennessee Biological and Small Molecule Mass Spectrometry Core (RRID: SCR_021368) using an UltiMate 3000 liquid chromatography system (Dionex, Sunnyvale, CA, USA) coupled to an Exactive Plus Orbitrap mass spectrometer (Thermo Fisher Scientific, Waltham, MA).

Sampleprep ID:

SP003150

Sampleprep Summary:

The metabolomic sample preparation method was: The tissue samples were ground into a homogenous powder with a Retsch Cryomill (Retsch-Allee, Haan, Germany). 45 – 80 mg of the pulverized sample was weighed and stored in the -80 oC freezer prior to extraction. Samples were allowed to thaw at 4 °C for 30 min before adding 1.5 mL of 20:40:40 water/methanol/acetonitrile with 0.1 M formic acid for metabolites extraction. The samples were vortexed and centrifuged and the supernatants were isolated and dried completely under nitrogen. The dried samples were resuspended in 300 µL water and an aliquot were transferred to autosampler vials for UHPLC-HRMS analysis. Mass analysis was carried out at the University of Tennessee Biological and Small Molecule Mass Spectrometry Core (RRID: SCR_021368) using an UltiMate 3000 liquid chromatography system (Dionex, Sunnyvale, CA, USA) coupled to an Exactive Plus Orbitrap mass spectrometer (Thermo Fisher Scientific, Waltham, MA).