α-melanocyte-stimulating hormone reduces impact of proinflammatory cytokine and peroxide-generated oxidative stress on keratinocyte and melanoma cell lines
α-melanocyte-stimulating hormone reduces impact of proinflammatory cytokine and peroxide-generated oxidative stress on keratinocyte and melanoma cell lines
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DOI：
10.1074/jbc.275.21.15629
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发表时间：
2000-05-26
影响因子：
4.8
通讯作者：
MacNeil, S
中科院分区：
文献类型：
--
作者：
Haycock, JW;Rowe, SJ;MacNeil, S
我们以前已经表明，或黑素细胞刺激激素（α-MSH）可以对抗肿瘤坏死因子（α激活NF-κ B（1-2小时）和细胞间粘附分子1的上调（3小时的mRNA和24小时的蛋白质）在黑素细胞和黑素瘤细胞。本研究报告的能力，四个MSH肽，以控制细胞内过氧化物水平和谷胱甘肽过氧化物酶（GPx）的活性在pigmentaries和nonpigmentaries细胞。在人HBL黑色素瘤和HaCaT角质形成细胞中，肿瘤坏死因子α和H2 O2均以时间和浓度依赖性方式（30-45分钟）激活GPx。发现α-MSH肽抑制刺激的GPx活性，并具有双相剂量-反应曲线。MSH 1-13和MSH [Nle（4）-D-Phe（7）]分别在10（-10）和10（-12）M时达到最大抑制。更高浓度（10-100倍）的MSH 4-10和MSH。需要11-13来产生同等水平的抑制。α-MSH也能够在15分钟内减少过氧化物的积累，并且这种抑制也是双相的。数据支持α-MSH在急性保护细胞免受NF-κ B和GPx活化之前的氧化/细胞因子作用中的作用。在色素细胞和非色素细胞中对α-MSH的反应的快速性和效力表明这是该肽在皮肤细胞中的核心作用。
We have previously shown that or-melanocyte-stimulating hormone (alpha-MSH) can oppose tumor necrosis factor (alpha activation of NF-KB (1-2 h) and intercellular adhesion molecule 1 up-regulation (mRNA by 3 h and protein by 24 h) in melanocytes and melanoma cells. The present study reports on the ability of four MSH peptides to control intracellular peroxide levels and glutathione peroxidase (GPx) activity in pigmentary and nonpigmentary cells. In human HBL melanoma and HaCaT keratinocytes tumor necrosis factor alpha and H2O2 both activated GPx in a time- and concentration-dependent manner (by 30-45 min). (alpha-MSH peptides were found to inhibit the stimulated GPx activity and had biphasic dose-response curves. MSH 1-13 and MSH [Nle(4)-D-Phe(7)] achieved maximum inhibition at 10(-10) and 10(-12) M, respectively. Higher concentrations (10-100 fold) of MSH 4-10 and MSH. 11-13 were required to produce equivalent levels of inhibition. alpha-MSH was also capable of reducing peroxide accumulation within 15 min, and again this inhibition was biphasic. The data support a role of (alpha-MSH in acute protection of cells to oxidative/cytokine action that precedes NF-kappa B and GPx activation. The rapidity and potency of the response to alpha-MSH in pigmentary and nonpigmentary cells suggest this to be a central role of this peptide in cutaneous cells.