Summary of project PR001386
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
| Project ID: | PR001386 |
| Project DOI: | doi: 10.21228/M8K11W |
| Project 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 |
| Project Type: | A Targeted Metabolomics Study |
| Project 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 |
| Email: | qzang@luc.edu |
| Phone: | 708-327-2472 |
| Funding Source: | This work is supported by Nathan Shock Center Pilot Award (to Q.S.Z.), National Institute of Health grant 2R01GM111295-01 (to Q.S.Z.), HL109471 and CA215063 (to Z.P.L.), R01HL158515 and R01GM124108 (to J.L.), R01AG049494 (to D.P), American Heart Association grant AHA 19TP34910172 (to Z.P.L., AND NIH P30 AG013280 (to the University of Washington Nathan Shock Center). We also acknowledge The Northwest Metabolomics Research Center at the University of Washington, Seattle, and NIH S10 Grant 1S10OD021562-01 (to D.R) that funded a purchase of the LC-MS system used to acquire targeted metabolomics data. |
| Contributors: | Matthew Kim, B.S, Azadeh Nikouee, PhD, Raymond Zou, Di Ren, PhD, Zhibin He, PhD, Ji Li, PhD, Lu Wang, PhD, Danijel Djukovic, PhD, Daniel Raftery, PhD, Hayley Purcell, B.S, Daniel Promislow, PhD, Yuxiao Sun, PhD, Mohammad Goodarzi, PhD, Qing-Jun Zhang, PhD, Zhi-Ping Liu, PhD, and Qun Sophia Zang, PhD |
Summary of all studies in project PR001386
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002178 | 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 | Mus musculus | Loyola University Chicago Stritch School of Medicine | MS | 2022-06-08 | 1 | 122 | Uploaded data (72.5M)* |
