Leptin-mediated gene-induction
    4.
    发明授权
    Leptin-mediated gene-induction 有权
    瘦蛋白介导的基因诱导

    公开(公告)号:US07291458B2

    公开(公告)日:2007-11-06

    申请号:US10235264

    申请日:2002-09-04

    IPC分类号: C12Q1/68

    摘要: Methods of activating a signaling cascade comprising, introducing leptin and/or a cytokine to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or acting on one or more downstream targets of adenylate cyclase, thereby inducing genes in neuro-endocrine cells or cells of neuro-endocrine origin. Two distinct gene-sets are induced, immediate early response genes (STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1), and late induced target genes (Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII). Strong co-stimulation with the adenylate cyclase activator forskolin was shown with respect to late induced target genes. Transcripts encoding Leptin Induced Protein I (LIP-I) and Leptin Induced Protein II (LIP-II) were identified; however, no forskolin co-stimulatory effect was observed. It is also demonstrated that leptin modulates in vivo expression of MT-II, Fnk and Pancreatitis Associated Protein I genes.

    摘要翻译: 激活信号级联的方法包括将瘦素和/或细胞因子引入到包含gp 130的受体复合物中,任选地与作用于腺苷酸环化酶的化合物组合或作用于腺苷酸环化酶的一个或多个下游靶标,从而诱导神经中的基因 内分泌细胞或神经内分泌源的细胞。 诱导两个不同的基因组,立即早期应答基因(STAT-3,SOCS-3,金属硫蛋白II,丝氨酸/苏氨酸激酶Fnk和MRF-1的大鼠同源物)和晚期诱导的靶基因(胰腺炎相关蛋白 I,角鲨烯环氧酶,二叉二磷酸葡糖醛酸转移酶和膜联蛋白VIII)。 与晚期诱导的靶基因相比,显示出与腺苷酸环化酶激活剂毛喉素的强共刺激。 鉴定了编码瘦素诱导蛋白I(LIP-I)和瘦蛋白诱导蛋白II(LIP-II)的转录物; 然而,没有观察到毛喉素共刺激作用。 还表明瘦素调节MT-II,Fnk和胰腺炎相关蛋白I基因的体内表达。