OMEGA 3 FATTY ACIDS IN GENE EXPRESSION AND APOPTOSIS

OMEGA 3 脂肪酸在基因表达和细胞凋亡中的作用

• 批准号: 2191737
• 负责人: ROGERS H LUMB
• 金额: $ 9.13万
• 依托单位: WESTERN CAROLINA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2191737
• 关键词: 1,25 dihydroxycholecalciferol; CD antigens; G protein; apoptosis; biological signal transduction; biomarker; cell differentiation; cell growth regulation; chemoattractants; cytokine receptors; diacylglycerols; dimethylsulfoxide; free fatty acids; gene expression; genetic transcription; immunoprecipitation; northern blottings; omega 3 fatty acid; phorbols; phosphatidate; platelet activating factor; protooncogene; retinoate; tissue /cell culture; transcription factor

DESCRIPTION: Diets rich in fatty acids of the n-3 family have positive health benefits in man including reduced cardiovascular problems and cancer incidence. There is some data to suggest that n-3 fatty acids are essential for normal human growth and development although the specific role played by n-3 fatty acids in cellular activities is completely unknown. The applicants have obtained evidence that docosahexaenoic acid (C22:6 n-3, DHA) has a direct effect on gene transcription in HL-60 cells, a human promyelocytic leukemia cell line. The effects of DHA include growth arrest, increased cell differentiation, and the disappearance of the c-myc proto-oncogene message. At higher concentrations DHA induces apoptosis in HL-60 cells, and might prove to be of considerable therapeutic value. It is their hypothesis that DHA affects cellular programs of differentiation and apoptosis by having an impact on gene transcription and entering signal transduction pathways. The projects described in this application are designed to test that hypothesis by; (1) determining what effects DHA has on programs of differentiation; (2) determining the effects of DHA on guanine nucleotide binding proteins (G-proteins); (3) determining which signal transduction pathways DHA participates in; and (4) determining the mechanisms by which DHA induces apoptosis.

描述：富含n-3家族脂肪酸的饮食具有积极的 对人类健康有益，包括减少心血管问题和癌症 发病率。 有一些数据表明n-3脂肪酸是必需的 正常的人类生长和发育，虽然发挥的具体作用， n-3脂肪酸在细胞中的活性是完全未知的。 的 申请人已经获得了二十二碳六烯酸（C22：6 n-3，DHA） 对人类HL-60细胞的基因转录有直接影响 早幼粒细胞白血病细胞系。 DHA的作用包括生长停滞， 细胞分化增加，c-myc消失， 原癌基因信息 在较高浓度下，DHA诱导细胞凋亡， HL-60细胞，并可能被证明是相当大的治疗价值。 是 他们假设DHA影响细胞的分化程序， 细胞凋亡通过影响基因转录和进入信号 转导途径。 本申请中描述的项目是 旨在通过以下方式验证这一假设：（1）确定DHA对 分化程序;（2）确定DHA对鸟嘌呤的影响 核苷酸结合蛋白（G蛋白）;（3）确定哪个信号 DHA参与的转导途径;和（4）确定 DHA诱导细胞凋亡的机制。