Summary of Study ST002178
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 PR001386. The data can be accessed directly via it's Project DOI: 10.21228/M8K11W 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.
| Study ID | ST002178 |
| Study Title | Age-independent Cardiac Protection by Pharmacological Activation of Beclin-1 During Endotoxemia and Its Association with Energy Metabolic Reprograming in Myocardium — A Targeted Metabolomics Study |
| Study Summary | Background: We previously showed that Beclin-1-dependent autophagy is cardiac protective in a rodent model of endotoxemia using young adult mice. In this report, we compared the potential therapeutic effects of pharmacological Beclin-1 activating peptide, TB-peptide, on the cardiac outcomes of young adult and aged mice during endotoxemia. We further examined alterations in myocardial metabolism induced by lipopolysaccharide (LPS) challenge with and without the TB-peptide treatment. Methods and Results: C57BL/6J mice of 10-week and 24-month-old were challenged by LPS at doses at which cardiac dysfunction occurred. Following the treatment of TB-peptide or control vehicle, heart contractility, circulating cytokines, and myocardial autophagy were evaluated. A targeted metabolomics assay was applied to analyze cardiac metabolism. TB-peptide boosted autophagic response, attenuated cytokine production, and improved cardiac performance in both young and aged mice during endotoxemia. A targeted metabolomics assay was designed to detect a pool of 361 known metabolites, of which 156 were detected in at least one of the heart tissue samples. LPS-induced impairments were found in glucose and amino acid (AA) metabolisms in mice of all ages, and TB-peptide provided ameliorative effects to rescue these alterations. However, lipid metabolites were upregulated in the young group but moderately downregulated in the aged by LPS, suggesting an age-dependent response. TB-peptide mitigated LPS-mediated trend of lipids in the young mice but provided little effect on the aged ones. Conclusion: Pharmacological activation of Beclin-1 by TB-peptide protects the heart in both young and aged population during endotoxemia, suggest a therapeutic potential for sepsis-induced cardiomyopathy. Metabolomics analysis suggests that this age-independent protection by TB-peptide is associated with reprograming of energy production via glucose and AA metabolisms. |
| Institute | Loyola University Chicago Stritch School of Medicine |
| Department | Surgery |
| Last Name | Zang |
| First Name | Qun |
| Address | 2160 S. 1st Ave, Maywood, IL 60153 |
| qzang@luc.edu | |
| Phone | 708-327-2472 |
| Submit Date | 2022-05-23 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-06-08 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003566 | AN003567 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Shimadzu Nexera X2 | Shimadzu Nexera X2 |
| Column | Waters XBridge BEH Amide (150 x 2.1mm,2.5um) | Waters XBridge BEH Amide (150 x 2.1mm,2.5um) |
| MS Type | ESI | ESI |
| MS instrument type | QTRAP | QTRAP |
| MS instrument name | ABI Sciex 6500+ | ABI Sciex 6500+ |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | count per second (cps) | count per second (CPS) |
MS:
| MS ID: | MS003323 |
| Analysis ID: | AN003566 |
| Instrument Name: | ABI Sciex 6500+ |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | MS data acquisition was performed in multiple-reaction-monitoring (MRM) mode. The whole LC-MS system was controlled using AB Sciex Analyst 1.6.3 software. Measured MS peaks were integrated using AB Sciex MultiQuant 3.0.3 software. In addition to the study samples, two sets of quality control (QC) samples were used to monitor the assay performance as well as data reproducibility. One QC was a pooled human serum sample used to monitor system performance and the other QC was pooled study samples and this QC was used to monitor data reproducibility. Isotope labeled compounds were used to monitor sample preparation and injection. Highly reproducible MS data were generated, having an average coefficient of variances (CVs) among the metabolites of 5.6%. Data for each sample were normalized according to bicinchoninic acid (BCA)-based quantification of total protein count. |
| Ion Mode: | POSITIVE |
| Analysis Protocol File: | Zang_Protocol.docx |
| MS ID: | MS003324 |
| Analysis ID: | AN003567 |
| Instrument Name: | ABI Sciex 6500+ |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | MS data acquisition was performed in multiple-reaction-monitoring (MRM) mode. The whole LC-MS system was controlled using AB Sciex Analyst 1.6.3 software. Measured MS peaks were integrated using AB Sciex MultiQuant 3.0.3 software. In addition to the study samples, two sets of quality control (QC) samples were used to monitor the assay performance as well as data reproducibility. One QC was a pooled human serum sample used to monitor system performance and the other QC was pooled study samples and this QC was used to monitor data reproducibility. Isotope labeled compounds were used to monitor sample preparation and injection. Highly reproducible MS data were generated, having an average coefficient of variances (CVs) among the metabolites of 5.6%. Data for each sample were normalized according to bicinchoninic acid (BCA)-based quantification of total protein count. |
| Ion Mode: | NEGATIVE |
| Analysis Protocol File: | Zang_Protocol.docx |
