Protein kinase CK2 impact on intracellular calcium homeostasis in prostate cancer.
Protein kinase CK2 impact on intracellular calcium homeostasis in prostate cancer.
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DOI：
10.1007/s11010-020-03752-4
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发表时间：
2020-07
影响因子：
4.3
通讯作者：
Ahmed K
中科院分区：
文献类型：
--
作者：
Afzal M;Kren BT;Naveed AK;Trembley JH;Ahmed K
蛋白激酶 CK2 在正常和疾病状态下的细胞功能中发挥多种作用。 CK2 在多种类型的癌细胞中升高，CK2 对细胞凋亡的抑制代表了癌细胞表型的关键联系。 CK2 对细胞存活和死亡的调节涉及多种过程，我们之前的工作表明线粒体机制是该功能的关键部位。前列腺细胞对 CK2 抑制的最早反应之一是线粒体膜电位的变化，可能与 Ca2+ 信号传导有关。因此，在目前的工作中，我们研究了 CK2 对细胞内 Ca2+ 动态的早期影响。研究了三种前列腺癌 (PCa) 细胞系：PC3-LN4、C4-2B 和 22Rv1。用 CK2 小分子抑制剂 4,5,6,7-四溴苯并三唑和 CX-4945 处理 PCa 细胞，然后分析不同细胞区室中 Ca2+ 水平随时间的变化。结果显示，胞浆 Ca2+ 水平在 2 分钟内开始出现剂量依赖性损失，并在 5-10 分钟内达到最大损失。内质网 (ER) 和线粒体区室中的 Ca2+ 也随之增加。结果表明，抑制 CK2 活性会导致 Ca2+ 快速移出细胞质并进入 ER 和线粒体，这可能是诱导受 CK2 抑制的细胞凋亡的最早影响因素之一。在具有诱导死亡水平的 CK2 抑制的细胞中，总细胞 Ca2+ 水平在治疗后 2 小时下降。这些新的观察结果代表了 CK2 活性调节细胞存活和死亡的潜在机制。
Protein kinase CK2 plays multiple roles in cell function in normal and disease states. CK2 is elevated in numerous types of cancer cells, and CK2 suppression of apoptosis represents a key link to the cancer cell phenotype. CK2 regulation of cell survival and death involves diverse processes, and our previous work suggested that mitochondrial machinery is a key locus of this function. One of the earliest responses of prostate cells to inhibition of CK2 is a change in mitochondrial membrane potential, possibly associated with Ca2+ signaling. Thus, in the present work, we investigated early impact of CK2 on intracellular Ca2+ dynamics. Three prostate cancer (PCa) cell lines, PC3-LN4, C4–2B, and 22Rv1, were studied. PCa cells were treated with the CK2 small molecule inhibitors 4,5,6,7-tetrabrombenzotriazole and CX-4945 followed by analysis of Ca2+ levels in various cellular compartments over time. The results showed dose-dependent loss in cytosolic Ca2+ levels starting within 2 min and reaching maximal loss within 5–10 min. There was a concomitant increase in Ca2+ in the endoplasmic reticulum (ER) and mitochondrial compartments. The results suggest that inhibition of CK2 activity results in a rapid movement of Ca2+ out of the cytosol and into the ER and mitochondria, which may be among the earliest contributory factors for induction of apoptosis in cells subjected to inhibition of CK2. In cells with death-inducing levels of CK2 inhibition, total cellular Ca2+ levels dropped at 2 h post-treatment. These novel observations represent a potential mechanism underlying regulation of cell survival and death by CK2 activity.
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影响因子：
4.7
作者：
Ivanova H;Kerkhofs M;La Rovere RM;Bultynck G
通讯作者：
Bultynck G
影响因子：
5.2
作者：
Ahmad, Kashif A.;Wang, Guixia;Ahmed, Khalil
通讯作者：
Ahmed, Khalil
影响因子：
4
作者：
Pinna, LA
通讯作者：
Pinna, LA
影响因子：
2.9
作者：
Arrigoni, G;Marin, O;Pinna, LA
通讯作者：
Pinna, LA
影响因子：
4.8
作者：
Hessenauer, Andrea;Schneider, Carolin C.;Montenarh, Mathias
通讯作者：
Montenarh, Mathias