Suhas K S, Parida Subhashree, Gokul Chandrasekaran, Srivastava Vivek, Prakash E, Chauhan Sakshi, Singh Thakur Uttam, Panigrahi Manjit, Telang Avinash G, Mishra Santosh K
Division of Pharmacology and Toxicology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
Division of Animal Genetics and Breeding, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India.
Exp Physiol. 2018 May 1;103(5):621-628. doi: 10.1113/EP086826. Epub 2018 Apr 15.
What is the central question of this study? Does the inhibition of the protein kinase casein kinase 2 (CK2) alter the uterine contractility? What is the main finding and its importance? Inhibition of CK2 impaired the spontaneous and oxytocin-induced contractility in late pregnant mouse uterus. This finding suggests that CK2 is a novel pathway mediating oxytocin-induced contractility in the uterus and thus opens up the possibility for this class of drugs to be developed as a new class of tocolytics.
The protein kinase casein kinase 2 (CK2) is a ubiquitously expressed serine or threonine kinase known to phosphorylate a number of substrates. The aim of this study was to assess the effect of CK2 inhibition on spontaneous and oxytocin-induced uterine contractions in 19 day pregnant mice. The CK2 inhibitor CX-4945 elicited a concentration-dependent relaxation in late pregnant mouse uterus. CX-4945 and another selective CK2 inhibitor, apigenin, also inhibited the oxytocin-induced contractile response in late pregnant uterine tissue. Apigenin also blunted the prostaglandin F response, but CX-4945 did not. Casein kinase 2 was located in the lipid raft fractions of the cell membrane, and disruption of lipid rafts was found to reverse its effect. The results of the present study suggest that CK2, located in lipid rafts of the cell membrane, is an active regulator of spontaneous and oxytocin-induced uterine contractions in the late pregnant mouse.
本研究的核心问题是什么？蛋白激酶酪蛋白激酶2（CK2）的抑制是否会改变子宫收缩力？主要发现及其重要性是什么？抑制CK2会损害妊娠晚期小鼠子宫的自发性收缩和催产素诱导的收缩。这一发现表明CK2是介导子宫中催产素诱导收缩的新途径，从而为这类药物开发成为新型宫缩抑制剂开辟了可能性。
蛋白激酶酪蛋白激酶2（CK2）是一种广泛表达的丝氨酸或苏氨酸激酶，已知可磷酸化多种底物。本研究的目的是评估抑制CK2对妊娠19天小鼠自发性和催产素诱导的子宫收缩的影响。CK2抑制剂CX-4945在妊娠晚期小鼠子宫中引起浓度依赖性舒张。CX-4945和另一种选择性CK2抑制剂芹菜素也抑制妊娠晚期子宫组织中催产素诱导的收缩反应。芹菜素也减弱了前列腺素F反应，但CX-4945没有。酪蛋白激酶2位于细胞膜的脂筏部分，发现破坏脂筏可逆转其作用。本研究结果表明，位于细胞膜脂筏中的CK2是妊娠晚期小鼠自发性和催产素诱导子宫收缩的活性调节因子。
