Summary of Study ST003222
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
| Study ID | ST003222 |
| Study Title | A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation - Part 1 |
| Study Summary | Microphage 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. This experimental is part of case 4535 showing the Lipidomics experimental data. |
| Institute | University of Mississippi Medical Center |
| Last Name | Li |
| First Name | Ji |
| Address | 2500 N State St, Jackson, MS 39216-4505 |
| jli3@umc.edu | |
| Phone | 6018158995 |
| Submit Date | 2023-12-14 |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-06-18 |
| Release Version | 1 |
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Treatment:
| Treatment ID: | TR003350 |
| Treatment Summary: | YWT: young wild type; Sham: no treatment; MIF20: treatment with MIF20; AWT: aged wild type; MIFff: with MIF; cMIFKO: knock out MIF; I/R: "ischemia-reperfusion"; For I/R, the myocardium underwent 45 minutes long ischemic condition, then followed by 24 hours long reperfusion. MIF20 was administered 5 minutes before the onset of reperfusion by I.V. injection via the jugular vein. MIF20 was administered until the MIF20 concentration in blood reached 8nM. Procedure is : We injected 100 uL of MIF20 solution (160 nM) into a mouse by I.V. Consider the total blood volume of a mouse is about 2 mL. Therefore, the MIF20 solution was diluted 20 times, reaching 8 nM in blood. |
