Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2021 Feb 10;11:3518. doi: 10.1038/s41598-021-81741-3

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

ADA-409-052 is protective against ferroptotic cell death in in vitro models of ferroptosis inducer class I and II. Increased cell viability, detected by the resazurin assay, illustrates the efficacy of ADA-409-052 on cultured PC-12 cells against either RSL3, a class II ferroptosis inducer inactivating GPx4, or glutamate, causing GSH depletion by inhibiting the system x_c⁻. (a) ADA-409-052 protects PC-12 cells against RSL3-induced (0.25 µM) ferroptotic cell death significantly at all given concentrations (ADA-409-052: 2.5–20 µM). (b) Low concentrations of minocycline (2.5 or 5 µM) were inefficient against RSL3-mediated cell death. However, concentrations of 10 and 20 µM significantly improved cell survival. One-way ANOVA followed by Tukey’s multiple comparison test; data are presented as percentage ± s.e.m.; technical n = 6; ***p < 0.0001. (c) ADA-409-052 (5–20 µM) prevented glutamate-induced (20 mM) ferroptotic cell death almost entirely. (d) Minocycline was only protective at concentrations of 10 and 20 µM. One-way ANOVA followed by Tukey’s multiple comparison test; data are presented as percentage ± s.e.m.; technical n = 6; ***p < 0.0001. (e,f) Glutamate-induced reduction of intracellular GSH-levels remains unchanged by ADA-409-052. Exposure of PC-12 cells to glutamate (20 mM) caused a major reduction of cell viability (f) and GSH levels (e) when compared with untreated control cells. While the cell viability was rescued almost entirely by the addition of ADA-409-052 (5 µM), the GSH levels remained comparable to glutamate-exposed cells. One-way ANOVA followed by Tukey’s multiple comparison test; data are presented as percentage ± s.e.m.; technical n = 6; **p = 0.0013; #p < 0.0001.