The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha.
The carboxyl-terminal cytoplasmic domain of CD36 is required for oxidized low-density lipoprotein modulation of NF-kappaB activity by tumor necrosis factor-alpha.
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发表时间：
1997
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通讯作者：
Robert Lipsky;D. Eckert;Y. Tang;C. Ockenhouse
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作者：
Robert Lipsky;D. Eckert;Y. Tang;C. Ockenhouse
氧化低密度脂蛋白（Ox LDL）与单核细胞-巨噬细胞的结合导致多效性效应，包括基因表达的变化，并被认为是动脉粥样硬化形成的早期事件。整合膜糖蛋白CD 36似乎在单核细胞-巨噬细胞结合和摄取Ox LDL中发挥生理作用，尽管与CD 36-Ox LDL相互作用相关的分子事件尚不清楚。为了解决这个问题，我们使用CD 36转染的中国仓鼠卵巢（CHO）细胞，暴露于Ox LDL，并确定转录因子NF-κ B活性的变化。我们在这里报告说，Ox LDL增强核提取物的DNA结合活性的NF-κ B序列后，激活的CD 36产生CHO细胞与促炎细胞因子肿瘤坏死因子-α（TNF-α）。这种增强的DNA结合活性通过将CD 36转染的细胞与人CD 36特异性抗体OKM 5共孵育来抑制。我们还确定NF-κ B DNA结合活性的激活需要CD 36上完整的羧基末端胞质片段。我们的研究结果支持的想法，人CD 36介导的信号转导事件响应于Ox LDL。
The binding of oxidized low-density lipoprotein (Ox LDL) by monocyte-macrophages causes pleiotropic effects, including changes in gene expression, and is thought to represent an early event in atherogenesis. The integral membrane glycoprotein CD36 appears to play a physiological role in binding and uptake of Ox LDL by monocyte-macrophages, although the molecular events associated with CD36-Ox LDL interaction are unknown. To approach this issue, we used CD36 transfected Chinese hampster ovary (CHO) cells, exposed them to Ox LDL, and determined changes in the activity of the transcription factor NF-kappaB. We report here that Ox LDL enhanced DNA binding activity of nuclear extracts to an NF-kappaB sequence following activation of CD36-producing CHO cells with the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). This enhanced DNA binding activity was inhibited by coincubation of CD36 transfected cells with the human CD36-specific antibody OKM5. We also determined that activation of NF-kappaB DNA binding activity required an intact carboxyl-terminal cytoplasmic segment on CD36. Our results support the idea that human CD36 mediates signal transduction events in response to Ox LDL.