Oxidative stress and ikBalpha modification

描述(由申请人提供) 转录因子NFkB是细胞反应中的关键因子 不同类型的压力。NFkB激活与细胞相关 增殖，出现在许多肿瘤中。调查人员已经证明 过氧化物酶增殖物，可引起氧化应激并起肝脏的作用 啮齿动物体内的致癌物可以激活肝脏中的NFkB。此激活可以 会被抗氧化剂阻挡。NFkB的激活是由一种信号介导的 导致磷酸化和随后的多泛素化的途径 和IKB的退化。最近，几个小组已经使用了体外系统 为了证明相扑可以以类似于以下方式与Ikba结合 该分子的多泛素化。这些研究提高了人们的兴趣 相扑修饰形式的Ikba可能参与了细胞内 对压力的反应。 研究人员已经发现了一种新的Ikba形式，它被发现在 用过氧化物酶增殖物治疗的小鼠的肝脏。这 改装与这是相扑改装的可能性一致 Ikba的形式。他们推测，这种新形式的Ikba可能是一种 肝组织中NFkB信号的重要调节因子 过氧化物酶增殖物。在这笔赠款中，他们建议将 过氧化酶体处理小鼠肝脏中IkBA的缓慢迁移形式 并确定这是否真的是相扑修改所致。 此外，由于这种新的Ikba形式是通过长期治疗 已知会导致氧化应激的过氧化物体增殖物， 调查人员将确定这种新的Ikba是否可以被 饮食抗氧化剂。总体而言，这些研究可能有助于阐明其他 生物体中控制NFkB活性的机制。

DESCRIPTION (provided by applicant) The transcription factor, NFkB, is a critical factor in the cellular response to various types of stress. NFkB activation is associated with cell proliferation and occurs in many tumors. The investigators have shown that peroxisome proliferators, which cause oxidative stress and act as hepatic carcinogens in rodents, can activate NFkB in the liver. This activation can be blocked by antioxidants. NFkB activation is mediated by a signaling pathway that leads to the phosphorylation and subsequent polyubiquitination and degradation of IkB. Recently, several groups have used in vitro systems to show that the SUMO can be conjugated to IkBa in a manner that is similar to polyubiquitination of this molecule. These studies raise the interesting possibility that SUMO-modified forms of IkBa may be involved in the cellular response to stress. The investigators have identified a novel form of IkBa that is found in the livers of mice that have been treated with peroxisome proliferators. This modification is consistent with the possibility that this is a SUMO-modified form of IkBa. They hypothesize that this novel form of IkBa may be an important regulator of NFkB signaling in the livers of mice treated with peroxisome proliferators. In this grant, they propose to characterize the slower migrating form of IkBa in the livers of mice treated with peroxisome proliferators and determine whether this indeed is due to SUMO-modification. In addition, since this novel IkBa form is induced by long-term treatment with peroxisome proliferators, which are known to cause oxidative stress, the investigators will determine whether this novel IkBa can be modulated by dietary antioxidants. Overall, these studies may help elucidate additional mechanisms that control NFkB activity in organisms.