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神经酰胺(ceramide,Cer)作为一种神经鞘磷脂分子,不仅是细胞膜的组成成分,而且可以作为各种信号转导途径的第二信使,参与细胞增殖、分化、衰老和凋亡等生命活动的调节。Cer的合成、代谢及信号转导在肿瘤发生发展甚至耐药和抵抗放射治疗中有着密切的关系。Cer可以被诸如肿瘤坏死因子α(Tumor necrosis factorα,TNF-α)、激素、电离辐射和化疗药物等细胞外信号和受体激活,其主要可以通过内源性凋亡途径和外源性凋亡途径诱导肿瘤细胞凋亡的发生。在肿瘤细胞凋亡发生过程中,Cer通过激活Jun氨基末端激酶(JNKs)、有丝分裂原活化蛋白激酶/细胞外信号调节蛋白激酶(MAPK/ERK)和P38等信号通路以及蛋白激酶、组织蛋白酶D、蛋白磷酸酶1(Protein phosphatase1,PP1)和蛋白磷酸酶2A(Protein phosphatase2A,PP2A)等效应分子介导肿瘤细胞凋亡。本文综述近年来有关Cer在应激反应级联以及肿瘤细胞凋亡中的作用的研究进展。
As a sphingomyelin molecule, ceramide (Cer) is not only a component of the cell membrane, but also serves as a second messenger of various signal transduction pathways involved in life activities such as cell proliferation, differentiation, senescence and apoptosis adjust. Cer synthesis, metabolism and signal transduction in tumor development and even resistance and resistance to radiation therapy are closely related. Cer can be activated by extracellular signals and receptors such as Tumor necrosis factor alpha (TNF-alpha), hormones, ionizing radiation and chemotherapeutic drugs, which can be mainly activated by endogenous apoptosis pathway and exogenous apoptosis Pathway to induce tumor cell apoptosis. In the process of tumor cell apoptosis, Cer through the activation of Jun N-terminal kinase (JNKs), mitogen activated protein kinase / extracellular signal-regulated protein kinase (MAPK / ERK) and P38 and other signaling pathways and protein kinase, cathepsin D, Protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) and other effector molecules mediate apoptosis of tumor cells. This review summarizes recent advances in the role of Cer in the stress response cascade and tumor cell apoptosis.