[Nle4, D-Phe7]-alpha-MSH: a superpotent melanotropin that "irreversibly" activates melanoma tyrosinase.
[Nle4, D-Phe7]-alpha-MSH: a superpotent melanotropin that "irreversibly" activates melanoma tyrosinase.
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[Nle4，D-Phe7]-α-MSH：一种超强促黑素，“不可逆”激活黑色素瘤酪氨酸酶。
DOI：
10.1080/07435808509032974
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发表时间：
1985
影响因子：
2.1
通讯作者：
Hruby,VJ
中科院分区：
文献类型：
--
作者：
Hadley,ME;AbdelMalek,ZA;Marwan,MM;Kreutzfeld,KL;Hruby,VJ
在Cloudman S91（CCL 53.1）黑色素瘤细胞系中研究了α-促黑素激素类似物[Nle 4，D-Phe]-α-MSH的超强效和超持久促黑素性质。[Nle4在刺激黑色素瘤细胞酪氨酸酶活性的刺激激素（α-MSH）中，D-Phe 7]-α-MSH比天然激素（α-MSH）有效100倍，根据其最小有效剂量（分别为10− 11 M和10− 9 M）确定。[Nle4在从孵育培养基中去除促黑素后，]-α-MSH对酪氨酸酶的作用也比α-MSH更持久。当细胞暴露于α-MSH（10− 7 M）24小时时，去除激素后的残留活性最小。与此相反，在相同的实验条件下，[Nle 4，D-Phe]-α-MSH处理诱导酪氨酸酶活性高于基础水平2-3倍，并保持显着的刺激作用，直到72小时后，去除促黑素激素。当促黑素暴露时间减少到4 h时，α-MSH不能引起显著的酪氨酸酶活性，而[Nle 4，D-Phe]-α-MSH在去除促黑素后的前24 h内刺激显著的酪氨酸酶活性。有趣的是，类似物的这种刺激在48小时增加，在去除促黑激素类似物后72小时达到最大值，并且在不存在类似物的情况下连续6天保持显著刺激。
The superpotent and ultraprolonged melanotropic properties of an α-melanotropin analog, [Nle4,D-Phe]-α-MSH, were investigated in a Cloudman S91 (CCL 53.1) melanoma cell line. [Nle4,D-Phe7]-α-MSH is 100-fold more effective than the native hormone, α-MSH), in stimulating hormone (α-MSH), in stimulating melanoma cell tyrosinase activity, as determined from their minimum effective doses (10−11M and 10−9M, respectively). [Nle4,D-Phe7]-α-MSH also exhibits a more sustained effect than α-MSH on tyrosinase after removal of the melanotropins from the incubation medium. When cells were exposed to α-MSH (10−7M) for 24 h, residual activity after removal of the hormone was minimally significant. In contrast, under the same experimental conditions [Nle4,D-Phe]-α-MSH treatment induced tyrosinase activity 2–3 fold above basal level, and maintained remarkable stimulatory effects up to 72 h following melanotropin removal. When the exposure time to melanotropins was reduced to 4 h, α-MSH failed to elicit significant tyrosinase activity, whereas [Nle4,D-Phe]-α-MSH stimulated significant tyrosinase activity during the first 24 h subsequent to melanotropin removal. Interestingly, this stimulation by the analog increased at 48 h, reached a maximum at 72 h following removal of the melanotropin analog, and remained significantly stimulated for 6 consecutive days in the absence of the analog.