Stimulation of S91 melanoma tyrosinase activity by superpotent alpha-melanotropins.
Stimulation of S91 melanoma tyrosinase activity by superpotent alpha-melanotropins.
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超强 α-促黑激素刺激 S91 黑色素瘤酪氨酸酶活性。
DOI：
10.1016/0303-7207(85)90020-6
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发表时间：
1985
影响因子：
4.1
通讯作者：
Castrucci,AM
中科院分区：
文献类型：
--
作者：
Marwan,MM;AbdelMalek,ZA;Kreutzfeld,KL;Hadley,ME;Wilkes,BC;Hruby,VJ;Castrucci,AM
研究了α-促黑素细胞激素（α-MSH，α-melanotropin）[Nle 4，D-Phe 7]-α-MSH及其类似物Ac-[Nle 4，D-Phe 7]-α-MSH 4 -11-NH 2和Ac-[Nle 4，D-Phe 7]-α-MSH 4 -10-NH 2对Cloudman S91小鼠黑色素瘤细胞酪氨酸酶活性的刺激作用。所有的促黑素素刺激酪氨酸酶活性的剂量依赖性的方式。[Nle4，D-Phe 7]-α-MSH的活性比a-MSH高约100倍，这是根据激活高于对照（基础）水平的酶所需的最小有效剂量（MED）确定的。该类似物在孵育24、48和72 h时显著刺激酪氨酸酶活性的MED为10− 11 M，而α-MSH在这些时间的MED均为10− 9 M。在存在[Nle 4，D-Phe 7]-α-MSH的情况下，从初始孵育时间起达到的最大酪氨酸酶活性在24、48和72 h分别约为对照水平的3倍、5倍和6倍。2个[Nle 4，D-Phe 7]-取代的片段类似物至少与十三肽类似物一样有活性，因此在刺激酶活性方面至少比α-MSH活性高100倍。这些[Nle 4，D-Phe 7]取代的类似物在黑色素瘤酪氨酸酶测定中比在黑色素瘤腺苷酸环化酶测定或其他正常黑色素细胞（青蛙和蜥蜴皮肤）生物测定中更有活性。
α-Melanocyte-stimulating hormone (α-MSH, α-melanotropin), [Nle4,D-Phe7]-α-MSH and related fragment analogues, Ac-[Nle4,D-Phe7]-α-MSH4–11-NH2and Ac-[Nle4,D-Phe7]-α-MSH4–10-NH2, were studied for their ability to stimulate tyrosinase activity in Cloudman S91 mouse melanoma cells in tissue culture. All of the melanotropins stimulated tyrosinase activity in a dose-dependent manner. [Nle4,D-Phe7]-α-MSH was about 100 times more active than a-MSH as determined from the minimal effective dose (MED) required to activate the enzyme above control (basal) levels. The MED of this analogue to significantly stimulate tyrosinase activity at 24, 48 and 72 h of incubation was 10−11M whereas the MED of α-MSH was 10−9M at each of these times. The maximum tyrosinase activity achieved from the time of initial incubation in the presence of [Nle4,D-Phe7]-α-MSH was approximately 3-, 5- and 6-fold greater than control levels at 24, 48 and 72 h, respectively. The 2 [Nle4,D-Phe7]-substituted fragment analogues were at least as active as the tridecapeptide analogue and therefore at least 100-fold more active than a-MSH in stimulating enzyme activity. These [Nle4,D-Phe7]-substituted analogues were more active in the melanoma tyrosinase assay than in the melanoma adenylate cyclase assay or other normal melanocyte (frog and lizard skin) bioassays.