Laboratory of Genetics, Academy of Zamosc, 22-400 Zamosc, Poland.
Institute of Nursing and Obstetrics, Academy of Zamosc, 22-400 Zamosc, Poland.
Genes (Basel). 2024 Mar 21;15(3):387. doi: 10.3390/genes15030387.
Multiple myeloma (MM) is a malignancy derived from plasma cells. Bortezomib affects the concentration of reduced glutathione (GSH) and the activity of glutathione enzymes. The aim of our study was to analyze deletion (null/present) variants of and genes and their association with the levels of glutathione and its enzymes in bortezomib-treated cell cultures derived from MM patients.
This study included 180 individuals (80 MM patients and 100 healthy blood donors) who were genotyped via multiplex PCR (for the / genes). Under in vitro conditions, MM bone marrow cells were treated with bortezomib (1-4 nM) to determine apoptosis (via fluorescence microscopy), GSH concentration, and activity of glutathione enzymes (via ELISA).
Bortezomib increased the number of apoptotic cells and decreased the activity of S-glutathione transferase (GST) and glutathione peroxidase (GPx). We found significant differences in GST activity between 1 nM (-null vs. -present), 2 nM (-null vs. -present), and 4 nM (-null vs. -present) bortezomib: 0.07 vs. 0.12, = 0.02; 0.06 vs. 0.10, = 0.02; and 0.03 vs. 0.08, = 0.01, respectively.
Bortezomib affects the activities of GST and GPx. GST activity was associated with and variants but only at some bortezomib doses.
多发性骨髓瘤（MM）是一种源自浆细胞的恶性肿瘤。硼替佐米会影响还原型谷胱甘肽（GSH）的浓度和谷胱甘肽酶的活性。我们研究的目的是分析硼替佐米治疗的 MM 患者骨髓细胞培养物中 和 基因缺失（null/present）变体及其与谷胱甘肽及其酶水平的关系。
本研究纳入了 180 名个体（80 名 MM 患者和 100 名健康献血者），通过多重 PCR（针对 和 基因）进行基因分型。在体外条件下，用硼替佐米（1-4 nM）处理 MM 骨髓细胞，通过荧光显微镜观察细胞凋亡，通过 ELISA 检测 GSH 浓度和谷胱甘肽酶的活性。
硼替佐米增加了凋亡细胞的数量，并降低了 S-谷胱甘肽转移酶（GST）和谷胱甘肽过氧化物酶（GPx）的活性。我们发现，在 1 nM（-null 与 -present）、2 nM（-null 与 -present）和 4 nM（-null 与 -present）硼替佐米处理时，GST 活性存在显著差异：0.07 与 0.12， = 0.02；0.06 与 0.10， = 0.02；0.03 与 0.08， = 0.01。
硼替佐米影响 GST 和 GPx 的活性。GST 活性与 和 变体有关，但仅在某些硼替佐米剂量下有关。
