Mode of Action of the Insect Hypertrehalosemic Hormone

这项研究将探讨与高海藻糖血症神经激素(HTH)诱导蟑螂脂肪体中细胞色素P450酶有关的生化机制。HTH是一种由神经细胞分泌的昆虫蛋白质激素，刺激脂肪体(=昆虫“肝”)将碳水化合物储存转化为血糖(海藻糖)。HTH还刺激P450酶家族中一个新成员的基因表达，在进化史上可以追溯到细菌和高等生物分化的时间。依赖HTH的P450的重要性将被评估，因为它与脂肪体代谢有关，P450基因将被分离和结构特征，以确定HTH如何控制其表达。蟑螂是最古老的生物之一，由于P450是最古老的基因之一，因此研究HTH对蟑螂脂肪体中P450基因表达的调控将有助于揭示高等动物起源时的基本细胞调控过程。从实用的角度来看，P450‘S是包括人类在内的所有动物代谢外来化学物质如药物、毒素、致癌物和杀虫剂的手段。由于这些化合物中的许多具有神经毒性，它们可能会刺激神经内分泌细胞释放激素，从而诱导P450合成，以促进毒物的代谢。因此，将神经激素与P450合成联系起来的研究可能会为人类对致癌物的反应和昆虫对杀虫剂的抗药性提供一个基本的解释。

The research will investigate biochemical mechanisms related to induction of a cytochrome P450 enzyme in the cockroach fat body by the hypertrehalosemic neurohormone (HTH) is an insect protein hormone secreted by nerve cells that stimulates the fat body (=insect "liver") to convert carbohydrate stores to blood sugar (trehalose). HTH also stimulates expression of a gene for a new member in a family of P450 enzymes traceable in evolution history to the time of divergence of bacteria and higher organisms. The significance of HTH-dependent P450 will be assessed as it relates to fat body metabolism, and the P450 gene will be isolated and structurally characterized to identify how HTH controls its expression. Cockroaches are one of the oldest living organisms, and since this P450 is one of the oldest genes, studies on HTH regulation of P450 gene expression in cockroach fat body will illuminate a fundamental cellular regulatory process that dates to the time of the origin of higher animals. From a practical view, P450's are the means by which all animals, including man, metabolize foreign chemicals such as drugs, toxins, carcinogens and insecticides. Since many of these compounds are neurotoxic, they may stimulate neuroendocrine cells to release hormones which induce P450 synthesis for metabolism of the toxicant. Therefore, studies linking neurohormones with P450 synthesis may provide a fundamental explanation for both man's response to carcinogens and insect resistance to insecticides.//