NONSTEROIDAL ANTIINFLAMMATORY DRUGS CAUSE APOPTOSIS AND INDUCE CYCLOOXYGENASES IN CHICKEN-EMBRYO FIBROBLASTS
NONSTEROIDAL ANTIINFLAMMATORY DRUGS CAUSE APOPTOSIS AND INDUCE CYCLOOXYGENASES IN CHICKEN-EMBRYO FIBROBLASTS
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DOI：
10.1073/pnas.92.17.7961
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
SIMMONS, DL
中科院分区：
文献类型：
--
作者：
LU, XJ;XIE, WL;SIMMONS, DL
程序性细胞死亡（凋亡）是生物体发育和衰老的内在组成部分。本文报道了许多非甾体类抗炎药（NSAID）在应用于v-src转化的鸡胚成纤维细胞（CEF）时引起凋亡。细胞死亡的特点是形态学的变化，组织转氨酶的诱导，和DNA的自消化。地塞米松，环氧化酶（考克斯）2的抑制剂，既不诱导细胞凋亡，也不改变NSAID的作用。前列腺素E（2），CEFs产生的主要类花生酸，也不能抑制细胞凋亡。原癌基因bcl-2的表达在CEFs中非常低，并且不被NSAID治疗改变。与此相反，p20，一种蛋白质，可以防止细胞凋亡时，成纤维细胞进入Go期，被强烈抑制。此处使用的NSAID浓度短暂抑制COX。然而，诱导了考克斯-1和考克斯-2 mRNA和考克斯-2蛋白。在某些细胞类型中，那么，慢性NSAID治疗可能导致考克斯活性增加，而不是降低，从而加剧了木兰素介导的炎症作用。考克斯-2转录物是先前描述的部分剪接和非功能性形式。因此，这些发现表明COX及其产物在预防CEF和其他细胞类型的细胞凋亡方面发挥着关键作用。
Programmed cell death (apoptosis) is an intrinsic part of organismal development and aging, Here we report that many nonsteroidal antiinflammatory drugs (NSAIDs) cause apoptosis when applied to v-src-transformed chicken embryo fibroblasts (CEFs). Cell death was characterized by morphological changes, the induction of tissue transglutaminase, and autodigestion of DNA. Dexamethasone, a repressor of cyclooxygenase (COX) 2, neither induced apoptosis nor altered the NSAID effect. Prostaglandin E(2), the primary eicosanoid made by CEFs, also failed to inhibit apoptosis. Expression of the protooncogene bcl-2 is very low in CEFs and is not altered by NSAID treatment. In contrast, p20, a protein that may protect against apoptosis when fibroblasts enter Go phase, was strongly repressed. The NSAID concentrations used here transiently inhibit COXs. Nevertheless, COX-1 and COX-2 mRNAs and COX-2 protein were induced, In some cell types, then, chronic NSAID treatment may lead to increased, rather than decreased, COX activity and, thus, exacerbate prostaglandin-mediated inflammatory effects. The COX-2 transcript is a partially spliced and nonfunctional form previously described. Thus, these findings suggest that COXs and their products play key roles in preventing apoptosis in CEFs and perhaps other cell types.