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To investigate the temporal association and molecular mechanism of bortezomib-induced mitochondrial oxidative stress and apoptosis in Schwann cells.
Rat Schwann RSC96 cells were cultured in vitro and treated with different concentrations of bortezomib to establish an in vitro model of bortezomib damaged RSC96 cells. The assessment of cell viability was conducted by means of the CCK-8 method, and the morphological alterations observed in each group of cells were documented through inverted microscope analysis. DCFH-DA and Hoechst staining were combined with fluorescence microscopy to determine the content of reactive oxygen species. JC-1 staining was used to detect mitochondrial membrane potential level, and the degree of mitochondrial permeability transition pore opening and Ca2+ concentration were detected by fluorescence microscope. Annexin V-FITC/PI dual labeling was used to detect cell apoptosis. ELISA was used to detect the levels of inflammatory factors TNF-α, IL-1β, and IL-6.
In comparison with the control group, as the bortezomib concentration increased, the viability of RSC96 cells decreased in a concentration-dependent manner. The cell gap increased, the number of cells decreased significantly, the nucleus solidified, and the cells exhibited typical characteristics of apoptosis. Furthermore, bortezomib induced a reactive oxygen species burst in RSC96 cells in a dose-dependent manner, resulting in depolarization of mitochondrial membrane potential, cytosolic Ca2+ overload, continuous opening of the mitochondrial permeability transition pore, and a significant increase in the apoptosis rate of RSC96 cells.
Bortezomib has been shown to induce programmed cell death apoptosis in Schwann cells by activating an axis involving oxidative stress, mitochondrial damage, and subsequent apoptosis. This finding suggests that oxidative stress and mitochondrial damage may represent pivotal mechanisms of bortezomib-induced toxicity, thus providing a novel target for the intervention of BIPN.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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