Tianeptine interferes with microtubule organization and hormone secretion of pheochromocytoma cells.
Tianeptine interferes with microtubule organization and hormone secretion of pheochromocytoma cells.
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噻奈普汀干扰嗜铬细胞瘤细胞的微管组织和激素分泌。
DOI：
10.1016/j.mce.2013.07.033
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发表时间：
2013
影响因子：
4.1
通讯作者：
Park,JoshuaJ
中科院分区：
文献类型：
--
作者：
Makani,Vishruti;Hall,James;Qamar,Khola;Jain,Priyanka;Jang,Yonggil;Hensley,Kenneth;Park,JoshuaJ
嗜铬细胞瘤起源于肾上腺髓质和交感神经节旁的嗜铬细胞。36-53%的嗜铬细胞瘤变成恶性的，并且此后对常规治疗有抗性。嗜铬细胞瘤也会引起引起严重高血压的儿茶酚胺分泌过多。我们发现，抗抑郁药噻奈普汀在临床剂量下可干扰嗜铬细胞瘤细胞的正常生命周期。在大鼠嗜铬细胞瘤PC 12细胞中，噻奈普汀治疗引起微管集束和细胞质动力蛋白的特异性降解，动力蛋白是一种逆行微管马达，在间期和有丝分裂期间介导各种微管依赖性过程。噻奈普汀还增加了促凋亡蛋白的水平，减缓了细胞周期进程，并增加了PC 12细胞的凋亡。重要的是，噻奈普汀治疗降低了高K+刺激的PC 12细胞中去甲肾上腺素和嗜铬粒蛋白A的分泌以及小鼠嗜铬细胞瘤MPC细胞中肾上腺素的分泌。我们的研究首次证明噻奈普汀干扰了嗜铬细胞瘤细胞的正常生命周期。
Pheochromocytoma originates from chromaffin cells in the adrenal medulla and sympathetic paraganglia. 36–53% of pheochromocytoma becomes malignant and, thereafter, resistant to conventional treatments. Pheochromocytoma also causes hyper-secretion of catecholamines that cause severe hypertension. We found that an antidepressant, tianeptine, interfered with normal life cycle of pheochromocytoma cells at its clinical doses. Treatment with tianeptine caused microtubule bundling and specific degradation of cytoplasmic dynein, a retrograde microtubule motor that mediates various microtubule-dependent processes during interphase and mitosis, in the rat pheochromocytoma PC12 cells. Tianeptine also increased the levels of pro-apoptotic proteins, slowed cell cycle progression, and increased apoptosis in PC12 cells. Importantly, tianeptine treatment decreased high K+-stimulated secretion of norepinephrine and chromogranin A in PC12 cells and of epinephrine in the mouse pheochromocytoma MPC cells. Our study demonstrates, for the first time, that tianeptine interferes with normal life cycle of pheochromocytoma cells.