PEROXISOME PROLIFERATOR INDUCED TRANSCRIPTION FACTORS

过氧化物酶体增殖物诱导的转录因子

• 批准号: 2802538
• 负责人: HOWARD P GLAUERT
• 金额: $ 7.26万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2802538
• 关键词: AP1 protein; DNA binding protein; NAD(H) phosphate; animal tissue; antioxidants; ascorbate; chemical carcinogen; chemical carcinogenesis; environmental toxicology; free radical oxygen; glutathione peroxidase; glutathione reductase; glutathione transferase; hamsters; laboratory rat; liver neoplasms; nuclear factor kappa beta; oxidative stress; peroxisome; species difference; stress proteins; superoxide dismutase; tocopherols; transcription factor

DESCRIPTION Hypolipidemic drugs, plasticizers, and other chemicals induce hepatic peroxisome proliferation and hepatocellular carcinomas in rats and mice. Other species, however, including Syrian hamsters, guinea pigs, and primates, have a lower response to peroxisome proliferators. The mechanisms by which these agents act in some species, but not in others, are unclear, but may be related to the induction of cell proliferation, the inhibition of apoptosis, or the production of active oxygen. The production of active oxygen could lead to changes in gene expression in the cell, including the activation of NF-kB in hamsters, a non responsive species. It is therefore hypothesized that the oxidative stress is important in the carcinogenic activity of peroxisome proliferators. The investigator proposes to examine 1) the levels of cellular antioxidants and antioxidant enzymes in rat and hamster liver to determine if differential reductions occur that may explain the activation of NF-kB in rats, but not hamsters, and 2) whether other active oxygen-induced transcription factors are also differentially activated in these two species. These studies will provide information that will address the long-term objective of determining the mechanisms of peroxisome proliferator-induced carcinogenesis.

描述 降血脂药物、增塑剂和其他化学物质会诱发肝病 大鼠和小鼠的过氧化物酶体增殖和肝细胞癌。 然而，其他物种，包括叙利亚仓鼠、豚鼠和 灵长类动物对过氧化物酶体增殖物的反应较低。 机制 这些药物在某些物种中起作用，但在其他物种中不起作用，尚不清楚， 但可能与诱导细胞增殖、抑制 细胞凋亡，或活性氧的产生。 活性物质的生产 氧气可能导致细胞内基因表达的变化，包括 仓鼠（一种非反应性物种）中 NF-kB 的激活。 因此是 推测氧化应激在致癌过程中起重要作用 过氧化物酶体增殖剂的活性。 调查员建议审查 1）大鼠体内细胞抗氧化剂和抗氧化酶的水平 仓鼠肝脏以确定是否发生差异减少可以解释 大鼠（而非仓鼠）中 NF-kB 的激活，以及 2) 是否有其他因素 活性氧诱导的转录因子也有差异 在这两个物种中被激活。 这些研究将提供以下信息： 将解决确定机制的长期目标 过氧化物酶体增殖物诱导的癌变。