| First Author | Inose-Maruyama A | Year | 2024 |
| Journal | Cell Stress Chaperones | Volume | 29 |
| Issue | 3 | Pages | 497-509 |
| PubMed ID | 38763404 | Mgi Jnum | J:352269 |
| Mgi Id | MGI:7705897 | Doi | 10.1016/j.cstres.2024.05.003 |
| Citation | Inose-Maruyama A, et al. (2024) Bag1 protein loss sensitizes mouse embryonic fibroblasts to glutathione depletion. Cell Stress Chaperones 29(3):497-509 |
| abstractText | Bcl2-associated athanogene-1 protein (Bag1) acts as a co-chaperone of heat shock protein 70 and heat shock cognate 70 and regulates multiple cellular processes, including cell proliferation, apoptosis, environmental stress response, and drug resistance. Since Bag1 knockout mice exhibited fetal lethality, the in vivo function of Bag1 remains unclear. In this study, we established a mouse line expressing Bag1 gene missing exon 5, which corresponds to an encoding region for the interface of heat shock protein 70/heat shock cognate 70. Despite mice carrying homoalleles of the Bag1 mutant (Bag1Îex5) expressing undetectable levels of Bag1, Bag1Îex5 homozygous mice developed without abnormalities. Bag1Îex5 protein was found to be highly unstable in cells and in vitro. We found that the growth of mouse embryonic fibroblasts derived from Bag1Îex5-homo mice was attenuated by doxorubicin and a glutathione (GSH) synthesis inhibitor, buthionine sulfoximine. In response to buthionine sulfoximine, Bag1Îex5-mouse embryonic fibroblasts exhibited a higher dropping rate of GSH relative to the oxidized glutathione level. In addition, Bag1 might mitigate cellular hydrogen peroxide levels. Taken together, our results demonstrate that the loss of Bag1 did not affect mouse development and that Bag1 is involved in intracellular GSH homeostasis, namely redox homeostasis. |
