Summary of Study ST001708
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 PR001093. The data can be accessed directly via it's Project DOI: 10.21228/M8DT31 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 | ST001708 |
| Study Title | Oxylipin biosynthesis reinforces cellular senescence through a RAS/p53 feedback loop and allows detection of senolysis |
| Study Summary | Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis |
| Institute | Buck Institute for Research on Aging |
| Last Name | Sharma |
| First Name | Rishi |
| Address | 8001 Redwood Blvd, Novato, CA, 94945, USA |
| sharmarishi2004@yahoo.co.in | |
| Phone | 5084392367 |
| Submit Date | 2021-02-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-08-10 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO001778 |
| Collection Summary: | Cell culture: Human fetal lung fibroblasts (IMR-90) and HEPG2 cells were cultured in Dulbecco’s modified eagle medium (DMEM - Gibco) supplemented with 10% FBS and penicillin/streptomycin (Gibco). HUVEC cells were obtained from the ATCC and cultured using the ATCC protocol and culture media. Quiescence was induced by replacing culture media with media containing 0.2% FBS for 72 h before analysis. All cells were cultured at 3% O2, and used prior to 40 population doublings, other than replicative senescent cells, which were cultured until replicative exhaustion. All cells were mycoplasma free. Mouse Plasma: Animal experiments were conducted using a protocol approved by the Institutional Animal Care and Use Committee of the Buck Institute. For DOXO treatments, 10-16 wk old p16-3MR mice received one intraperitoneal (i.p.) injection of 10 mg/kg of doxorubicin hydrochloride in PBS, and treated 5 d later with GCV or vehicle. GCV was administered via daily i.p. injections for 5 consecutive days at 25 mg/kg in PBS. Control mice were injected with an equal volume of PBS. Mice were euthanized and tissues collected 10 d after DOXO challenge. For aging studies, C57BL/6 mice were aged for 6 or 24 mo, at which point mice were euthanized and tissues collected for analysis. For the biomarker studies, mice with challenged with DOXO as above, and given either vehicle or ABT-263 6 weeks after DOXO challenge. Whole blood was collected by cardiac puncture into EDTA-tubes (lavender caps – BD Biosciences) and spun at 2000g for 5 minutes. For urine collection, mice were placed in plastic containers prior to euthanasia. |
| Sample Type: | Blood (plasma) |
