REGULATION OF CELL GROWTH BY LINOLEIC ACID METABOLITES IN SHE CELLS

SHE细胞中亚油酸代谢物对细胞生长的调节

• 批准号: 6106723
• 负责人: T ELING
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6106723
• 关键词: apoptosis; cell growth regulation; embryo /fetus tissue /cell culture; embryogenesis; enzyme activity; epidermal growth factor; hamsters; linoleate; lipid metabolism; lipoxygenase; mammalian embryology

Summary of Work: We have used Syrian hamster embryo cells (SHE) to study the modulation of cell growth and apoptosis by lipid metabolites. EGF-dependent mitogenesis was inhibited by lipoxygenase inhibitors, but not attenuated by PGHS inhibitors. EGF did not stimulate prostaglandin formation, but did stimulate the metabolism of linoleic acid to 13(S)-HODE. The formation of 13-HODE is regulated by the tyrosine kinase activity of the EGF receptor, but the mechanism is poorly understood. The linoleic acid metabolite potentiated EGF-dependent mitogenesis in the supB+ SHE cells, but this response was lost on progression to the supB-. Structure-activity investigations revealed that 13(S)-HpODE was the most effective lipid compound in stimulating EGF-regulated DNA synthesis in SHE cells. This suggested a specific site for 13(S)-HpODE effects. Since the formation of 13(S)-HpODE up-regulates EGF-dependent cell growth, we prepared stable transfectants of supB+ cells that over-express 15-LO. This increased expression of 15-lipoxygenase and formation of 13 (S)-HpODE increases the rate of cell growth 4 fold. These findings provide additional evidence for lipid metabolites as regulators of cell proliferation.

工作总结：我们使用了叙利亚仓鼠 胚胎细胞（SHE）用于研究细胞生长的调节和 脂质代谢导致的细胞凋亡。 EGF依赖性有丝分裂发生 被脂氧合酶抑制剂抑制，但不被 PGHS 减弱 抑制剂。 EGF 不会刺激前列腺素的形成，但会刺激前列腺素的形成。 刺激亚油酸代谢为13(S)-HODE。这 13-HODE 的形成受酪氨酸激酶活性调节 EGF 受体的作用，但其机制尚不清楚。这 亚油酸代谢物增强 EGF 依赖性有丝分裂 suB+ SHE 细胞，但这种反应在进展到 支持B-。结构-活性研究表明 13(S)-HpODE 是最有效的脂质化合物 刺激 SHE 细胞中 EGF 调节的 DNA 合成。这 建议 13(S)-HpODE 效应的特定位点。自从 13(S)-HpODE 的形成上调 EGF 依赖性细胞 生长，我们制备了supB+细胞的稳定转染子 过度表达 15-LO。这增加了 15-脂氧合酶的表达 13 (S)-HpODE 的形成可提高细胞生长速度 4 折叠。这些发现为脂质提供了额外的证据 代谢物作为细胞增殖的调节剂。