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首页> 外文期刊>Biochemical Pharmacology >Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness.
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Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness.

机译：与神经性厌食症和肥胖相关的刺豚鼠相关蛋白中Ala67Thr多态性的功能分析。

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摘要

AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions.
机译：AgRP是一种神经肽，可通过抑制中枢黑皮质素受体（MCR）刺激食物摄入。在人类中，非保守氨基酸取代丙氨酸（Ala）67苏氨酸（Thr）与神经性厌食症和肥胖相关。在本研究中，研究了Ala67和Thr67 AgRP的细胞分布，加工以及体外和体内活性。用Ala67或Thr67表达构建体稳定转染的BHK细胞的培养基和裂解物的Western印迹显示相同的AgRP条带。当在Att20 D16V细胞中表达时，Ala67和Thr67 AgRP都与高尔基体共定位，但与ER或溶酶体共定位。同样，在报告基因试验中细菌表达的Ala67和Thr67 AgRP刺激MC4R或抑制大鼠食物摄取的效力之间未观察到差异。两者合计，没有证据表明与MC4R相互作用有关的Thr67 AgRP功能缺陷。

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