Platycodin D-induced apoptosis through nuclear factor-κB activation in immortalized keratinocytes
Platycodin D-induced apoptosis through nuclear factor-κB activation in immortalized keratinocytes
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DOI：
10.1016/j.ejphar.2006.03.012
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发表时间：
2006-05-10
影响因子：
5
通讯作者：
Kim, Yeong Shik
中科院分区：
文献类型：
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作者：
Ahn, Kwang Seok;Hahn, Bum-Soo;Kim, Yeong Shik
桔梗是桔梗的根，在传统的东方医学中被广泛用作肺部疾病的祛痰剂和呼吸系统疾病的治疗剂。桔梗皂苷D是桔梗中三萜皂苷的主要成分。本研究探讨凋亡的桔梗皂苷D在永生化的人角质形成细胞（HaCaT）。通过DNA片段化、半胱天冬酶-3活化和半胱天冬酶-8活化证实了桔梗皂苷D诱导的HaCaT细胞凋亡。桔梗皂苷D可激活核因子-κ B激酶（IKK）抑制剂-β在核因子-κ B（NF-κ B）上游水平的激活，而对IKK-α无激活作用。NF-κ B抑制剂预处理的N-甲苯磺酰基-L-苯丙氨酸氯甲基酮（TPCK）可抑制桔梗皂苷D诱导HaCaT细胞凋亡和NF-κ B活化。我们还表明，桔梗皂苷D介导的HaCaT细胞凋亡上调Fas受体和Fas配体（FasL）的表达。但未显示p53活化。用pFLF 1转染HaCaT细胞，该pFLF 1保留了含有NF-κ B结合位点的Fas受体基因的启动子区。与桔梗皂苷D孵育后，与Fas受体相关的NF-κ B活性以剂量依赖性方式增加。在Fas受体和FasL启动子上的主要转录元件中，NF-κ B B活化被证明在死亡受体如FasL的表达中具有重要作用。这些结果表明，桔梗皂苷D具有诱导HaCaT细胞凋亡的能力，通过上调Fas受体和FasL的表达，在转录水平上通过NF-κ B活化。这些结果表明，NF-κ B活化在用桔梗皂苷D处理的人HaCaT细胞中诱导凋亡中起关键作用。(c)2006 Elsevier B. V.保留所有权利。
Platycodi Radix is the root of Platycodon grandiflorum and it is widely used in the traditional Oriental medicine as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Platycodin D is the major constituent of triterpene saponins in the root. This study investigates apoptosis by platycodin D in immortalized human keratinocytes (HaCaT). Platycodin D-induced apoptosis in HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase-8 activation. Platycodin D could activate inhibitor of nuclear factor-kappa B kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappa B) activation of upstream level, but not IKK-alpha. Pretreated-N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a potent NF-kappa B inhibitor, could suppress the induction of apoptosis and activation of NF-kappa B of HaCaT cells by platycodin D. We also demonstrated that platycodin D-mediated apoptosis of HaCaT cells upregulates Fas receptor and Fas ligand (FasL) expression. but did not exhibit p53 activation. HaCaT cells were also transfected with pFLF1, which preserves the promoter region of Fas receptor gene containing NF-kappa B binding site. On incubation with platycodin D, the NF-kappa B activity related to Fas receptor increased in a dose-dependent manner. Among the major transcription elements on Fas receptor and FasL promoter, NF-kappa B activation was shown to have an essential role in the expression of the death receptor such as FasL. These results suggest that platycodin D has the ability to induce apoptosis in HaCaT cells through the upregulation of Fas receptor and FasL expression via to NF-kappa B activation in the transcriptional level. These results demonstrate that the NF-kappa B activation plays a crucial role in the induction of apoptosis in human HaCaT cells on treatment with platycodin D. (c) 2006 Elsevier B.V. All rights reserved.