| 第一作者： | Hekmatara, M (Hekmatara, Maryam); Baladehi, MH (Baladehi, Mohammadhadi Heidari); Ji, YT (Ji, Yuetong); Xu, J (Xu, Jian); |
|---|---|
| 联系作者： | Hekmatara, M (Hekmatara, Maryam); Baladehi, MH (Baladehi, Mohammadhadi Heidari); Ji, YT (Ji, Yuetong); Xu, J (Xu, Jian); |
| 发表年度： | 2021 |
| 期： | 4 |
| 卷： | 93 |
| 页： | 2125-2134 |
| 摘要： | To profile the metabolic dynamics responding to drugs at the single-cell/organelle resolution, rapid and economical mechanism-revealing methods are required. Here, we introduced D2O-probed Raman microspectroscopy in combination with the multivariate curve resolution-alternating least squares (MCR-ALS or MCR) algorithm. Exploiting MCR to deconvolute each macromolecular component specifically, the method is able to track and distinguish changes in lipid and protein metabolic activities in a human cancer cell line (MCF-7) and in Saccharomyces cerevisiae, in response to the metabolism-inhibitory effect of rapamycin, which inhibits the mammalian/mechanistic target of rapamycin (mTOR) signaling. Under rapamycin, in the lipid bodies of cancer cells, metabolic activities of both protein and lipid are suppressed; in the nucleus, protein synthesis remains active, whereas lipid synthesis is inhibited; in the cytoplasm, syntheses of protein and lipid are both dose- and duration-dependent. Thus, rapamycin differentially influences protein and lipid synthesis in mTOR signaling. Moreover, the strong correlation between macromolecular-specific components of yeast and those in MCF-7 cytoplasm, nucleus, and lipid bodies revealed similarity in rapamycin response. Notably, highly metabolically active cancer cells after high-dosage rapamycin exposure (500 or 5000 X IC50) were revealed, which escape detection by population-level cytotoxicity tests. Thus, by unveiling macromolecule-specific metabolic dynamics at the organelle level, the method is valuable to mechanism-based rapid screening and dissection of drug response. |
| 刊物名称： | ANALYTICAL CHEMISTRY |
| 影响因子： | 6.35 |
| 全文链接： | https://pubs.acs.org/doi/10.1021/acs.analchem.0c03925 |
