Oxidative stress activates a redox-sensitive PI3K-AKT-mTORC1-eIF4A cascade that selectively promotes P-glycoprotein translation via cap-dependent mRNA engagement, revealing a transcription-independent mechanism of rapid multidrug resistance induction.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Cell line |
| Journal | Free radical biology & medicine |
| Year | 2026 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.freeradbiomed.2026.07.033 |
Cells face a temporal gap in oxidative stress adaptation, in which acute insults require rapid protein synthesis before transcriptional responses are fully established. Low-dose glucosamine (GlcN) induces a transient intracellular oxidation-sensitive response and activates redox-sensitive PI3K-AKT-mTORC1 signaling, leading to increased P-glycoprotein (P-gp) abundance without a detectable increase in total ABCB1 mRNA.
| Intervention | Glucosamine; redox stress |
| Target | mTORC1 / eIF4A / 4E-BP1 |
| Model | Cell line |
| Effect | mTOR-eIF4A selectively upregulates P-gp translation under oxidative stress; multidrug resistance |