Cloning of a human Bcl-2 homologue: Inflammatory cytokines induce human A1 in cultured endothelial cells
Cloning of a human Bcl-2 homologue: Inflammatory cytokines induce human A1 in cultured endothelial cells
复制标题
DOI：
10.1182/blood.v87.8.3089.bloodjournal8783089
复制
发表时间：
1996-04-15
期刊：
影响因子：
20.3
通讯作者：
Harlan, JM
中科院分区：
文献类型：
--
作者：
Karsan, A;Yee, E;Harlan, JM
Bcl-2是一种细胞内膜相关蛋白，其功能是阻止程序性细胞死亡。尽管反复暴露于循环和组织中的细胞毒素，内皮细胞对细胞死亡具有显著的抵抗力。由于内皮细胞中的Bcl-2蛋白水平较低或无法检测到，我们假设内皮细胞中存在生长中的Bcl-2家族的其他成员，以防止细胞凋亡。利用Bcl-2家族两个保守区域的简并引物在内皮细胞中扩增潜在的同源物。这一策略导致分离出与小鼠A1相关的人类Bcl-2同源物，A1是该家族最近发现的成员。我们在这里表明，在内皮细胞中，人A1可以被phorbol酯和炎症细胞因子、肿瘤坏死因子- α和白细胞介素-1 β快速诱导，但不能被生长因子、碱性成纤维细胞生长因子或血管内皮生长因子诱导。A1是已知唯一可被炎症因子诱导的Bcl-2家族成员，提示其可能在炎症过程中发挥保护作用。此外，血管平滑肌细胞和各种非造血组织表达人A1，表明人A1是广泛表达的Bcl-2同源物。(C) 1996年由美国血液病学会出版。
Bcl-2 is an intracellular membrane-associated protein that functions to block programmed cell death. Despite recurrent exposure to cellular toxins from the circulation and tissue, endothelial cells are remarkably resistant to cell death. Because Bcl-2 protein levels are low or undetectable in endothelial cells, we postulated that other members of the growing Bcl-2 family would be present in endothelial cells to provide protection against apoptosis. Degenerate primers to two conserved regions of the Bcl-2 family were used to amplify potential homologues in endothelial cells. This strategy resulted in the isolation of a human Bcl-2 homologue related to murine A1, a recently identified member of this family. We show here that, in endothelial cells, human A1 is rapidly inducible by phorbol ester and the inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1 beta, but not by the growth factors, basic fibroblast growth factor or vascular endothelial growth factor. A1 is the only known Bcl-2 family member that is inducible by inflammatory cytokines, suggesting that it may play a protective role during inflammation. Additionally, vascular smooth muscle cells and various nonhematopoietic tissues express human A1, indicating that human A1 is a widely expressed Bcl-2 homologue. (C) 1996 by The American Society of Hematology.