PKC-ζ 在 U46619 通过 NADPH 氧化酶-PKCα-Giα 轴抑制肺动脉平滑肌细胞 β-肾上腺素能反应中的作用。
Role of PKC-ζ in NADPH oxidase-PKCα-Giα axis dependent inhibition of β-adrenergic response by U46619 in pulmonary artery smooth muscle cells.
机构信息
Department of Biochemistry and Biophysics, University of Kalyani, Nadia 741235, West Bengal, India.
出版信息
Arch Biochem Biophys. 2013 Dec;540(1-2):133-44. doi: 10.1016/j.abb.2013.10.018. Epub 2013 Oct 30.
Treatment of bovine pulmonary artery smooth muscle cells (BPASMCs) with U46619 attenuated isoproterenol caused stimulation of adenyl cyclase activity and cAMP production. Pretreatment with SQ29548 (Tp receptor antagonist), apocynin (NADPH oxidase inhibitor) and Go6976 (PKC-α inhibitor) eliminated U46619 caused attenuation of isoproterenol stimulated adenyl cyclase activity. Pretreatment with SQ29548 and apocynin prevented U46619 induced increase in NADPH oxidase activity, PKC-α activity and Giα phosphorylation. However, pretreatment with CZI, a PKC-ζ inhibitor, markedly, but not completely, inhibited U46619 induced increase in NADPH oxidase activity, PKC-α activity, Giα phosphorylation and also significantly eliminated U46619 caused attenuation of isoproterenol stimulated adenyl cyclase activity. Pretreatment with Go6976 inhibited U46619 induced increase in Giα phosphorylation, but not PKC-ζ activity and NADPH oxidase activity. Pretreatment with pertussis toxin eliminated U46619 caused attenuation of isoproterenol stimulated adenyl cyclase activity without any discernible change in PKC-ζ, NADPH oxidase and PKC-α activities. Transfection of the cells with Tp, PKC-ζ and PKC-α siRNA duplexes corroborate the findings observed with their respective pharmacological inhibitors on the responses produced by U46619. Taken together, we suggest involvement of PKC-ζ in U46619 caused attenuation of isoproterenol stimulated β-adrenergic response, which is regulated by NADPH oxidase-PKCα-Giα axis in pulmonary artery smooth muscle cells.
用 U46619 处理牛肺动脉平滑肌细胞（BPASMCs）可减轻异丙肾上腺素引起的腺苷酸环化酶活性和 cAMP 产生的刺激。用 SQ29548（Tp 受体拮抗剂）、阿朴肉桂酸（NADPH 氧化酶抑制剂）和 Go6976（PKC-α 抑制剂）预处理可消除 U46619 引起的异丙肾上腺素刺激的腺苷酸环化酶活性减弱。用 SQ29548 和阿朴肉桂酸预处理可防止 U46619 诱导的 NADPH 氧化酶活性、PKC-α 活性和 Giα 磷酸化增加。然而，PKC-ζ 抑制剂 CZI 的预处理显著但不完全抑制 U46619 诱导的 NADPH 氧化酶活性、PKC-α 活性、Giα 磷酸化增加，也显著消除 U46619 引起的异丙肾上腺素刺激的腺苷酸环化酶活性减弱。用 Go6976 预处理可抑制 U46619 诱导的 Giα 磷酸化增加，但不抑制 PKC-ζ 活性和 NADPH 氧化酶活性。百日咳毒素预处理消除了 U46619 引起的异丙肾上腺素刺激的腺苷酸环化酶活性减弱，而对 PKC-ζ、NADPH 氧化酶和 PKC-α 活性没有任何明显改变。用 Tp、PKC-ζ 和 PKC-α siRNA 双链体转染细胞证实了它们各自的药理学抑制剂对 U46619 产生的反应的发现。总之，我们认为 PKC-ζ 参与了 U46619 引起的异丙肾上腺素刺激的β-肾上腺素能反应的减弱，该反应受肺动脉平滑肌细胞中 NADPH 氧化酶-PKCα-Giα 轴的调节。
Zotero 插件