Morphine induces DNA damage and P53 activation in CD3+ T cells.
Morphine induces DNA damage and P53 activation in CD3+ T cells.
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DOI：
10.1016/j.bbagen.2009.04.011
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发表时间：
2009-08
期刊：
影响因子：
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通讯作者：
H. Tsujikawa;T. Shoda;T. Mizota;K. Fukuda
中科院分区：
文献类型：
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作者：
H. Tsujikawa;T. Shoda;T. Mizota;K. Fukuda
背景：吗啡对免疫系统功能的影响已被证实，但其确切机制尚不清楚。本研究旨在通过分析吗啡对人CD3+T细胞的直接作用，阐明吗啡诱导免疫抑制的机制。方法为了鉴定吗啡对CD3+T细胞中阿片受体表达上调的基因，采用纳洛酮存在和不存在情况下吗啡处理的人CD3+T细胞的总RNA进行pcr选择cDNA减法。结果我们发现p53和损伤特异性DNA结合蛋白2 （ddb2）基因在吗啡作用下以纳洛酮敏感的方式上调。此外，结果表明，通过apur尿酸- ap嘧啶位点计数和P53蛋白Ser-15的磷酸化，吗啡在CD3+T细胞中以纳洛酮敏感的方式诱导DNA损伤。由于阿片受体家族中只有κ阿片受体基因在CD3+T细胞中表达，本研究提示吗啡通过作用于κ阿片受体诱导DNA损伤，通过激活p53介导的信号转导导致免疫抑制。
BACKGROUNDMorphine has been shown to affect the function of immune system, but the precise mechanism remains to be elucidated. The present study was aimed to clarify the mechanism for the morphine-induced immune suppression by analyzing the direct effect of morphine on human CD3+T cells.METHODSTo identify genes up-regulated by action of morphine on the opioid receptor expressed in CD3+T cells, PCR-select cDNA subtraction was performed by the use of total RNA from human CD3+T cells treated with morphine in the presence and absence of naloxone.RESULTSWe show that p53 and damage-specific DNA binding protein 2 (ddb2) genes are up-regulated by morphine in a naloxone-sensitive manner. Furthermore, the results indicate that DNA damage, quantified by apurinic–apyrimidinic site counting assay and phosphorylation of Ser-15 in P53 protein, is induced in CD3+T cells by morphine in a naloxone-sensitive manner.GENERAL SIGNIFICANCEBecause it was shown that only the κ opioid receptor gene is expressed in CD3+T cells in the opioid receptor family, the present study suggests that morphine induces DNA damage through the action on the κ opioid receptor, which leads to immune suppression by activation of P53-mediated signal transduction.