Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness.
Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness.
复制标题
与神经性厌食症和瘦弱相关的刺鼠相关蛋白中 Ala67Thr 多态性的功能分析。
DOI：
10.1016/j.bcp.2005.04.033
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发表时间：
2005
影响因子：
5.8
通讯作者：
Adan,RogerAH
中科院分区：
文献类型：
--
作者：
deRijke,CorineE;Jackson,PilgrimJ;Garner,KeithM;vanRozen,ReaJ;Douglas,NickR;Kas,MartienJH;Millhauser,GlennL;Adan,RogerAH
AgRP是一种神经肽，通过抑制中央黑素皮质素受体（mcr）来刺激食物摄入。在人类中，非保守氨基酸取代丙氨酸（Ala） 67苏氨酸（Thr）与神经性厌食症和消瘦有关。本研究对Ala67和Thr67 AgRP的细胞分布、加工过程及体内外活性进行了研究。稳定转染Ala67或Thr67表达构建体的BHK细胞培养基和裂解物的Western blots显示相同的AgRP条带。在at20 D16V细胞中表达时，Ala67和Thr67 AgRP均与高尔基体共定位，但不与内质网或溶酶体共定位。此外，在报告基因试验中，细菌表达的Ala67和Thr67 AgRP在刺激MC4R或抑制大鼠食物摄入方面没有发现差异。综上所述，没有证据表明Thr67 AgRP的功能缺陷与MC4R相互作用有关。
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.