Melatonin as antioxidant, geroprotector and anticarcinogen
Melatonin as antioxidant, geroprotector and anticarcinogen
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DOI：
10.1016/j.bbabio.2006.03.012
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发表时间：
2006-05-01
影响因子：
4.3
通讯作者：
Vinogradova, Irina A.
中科院分区：
文献类型：
--
作者：
Anisimov, Vladimir N.;Popovich, Irina G.;Vinogradova, Irina A.
人们已经使用各种方法研究了松果体吲哚激素褪黑激素对小鼠、大鼠和果蝇寿命的影响。已经观察到，在雌性CBA、SHR、SAM和转基因HER-2/neu小鼠中，长期施用褪黑激素后平均寿命增加。在大鼠中，褪黑激素治疗增加了雄性和雌性大鼠的存活率。in d.在黑腹果蝇中，在发育阶段将褪黑激素补充到营养培养基中产生了矛盾的结果，但是当褪黑激素在整个生命周期中被添加到食物中时，已经观察到果蝇的寿命增加。在小鼠和大鼠中，褪黑激素在体外和体内都是一种有效的抗氧化剂。单独的褪黑激素在艾姆斯试验中既无毒性也无致突变性，在COMET试验中显示高浓度下的致染色体断裂活性。褪黑激素具有抑制多种间接化学诱变剂的诱变和致染色体断裂作用。褪黑激素可抑制啮齿类动物自发性和7 - 1,2-二甲基苯蒽（DMBA）或N-亚硝基甲基脲诱导的乳腺癌发生;抑制1，2-二甲基肼诱导的大鼠结肠癌发生;抑制N-二乙基亚硝胺诱导的大鼠肝癌发生;抑制DMBA诱导的小鼠宫颈和阴道癌发生;抑制苯并（a）芘诱导的软组织癌发生;抑制乌拉坦诱导的小鼠肺癌发生。为了鉴定褪黑激素调节的分子事件，使用cDNA基因表达阵列（分别为15，247和16，897个cDNA克隆集）研究褪黑激素处理的CBA小鼠的心脏和大脑中的基因表达谱。研究表明，控制细胞周期、细胞/生物体防御、蛋白质表达和转运的基因是褪黑激素的主要效应子。褪黑激素还增加了一些线粒体基因（16 S、细胞色素c氧化酶I和3（考克斯I和COX 3）以及NADH氧化酶I和4（ND 1和ND 4））的表达，这与其抑制自由基过程的能力一致。最令人感兴趣的是褪黑激素对大量与钙交换相关的基因（如Cu15、Dcamk11和Kcnn 4）表达的影响;还检测到褪黑激素对一些致癌相关基因表达的显著影响。因此，我们认为褪黑激素可用于预防过早衰老和致癌。(c)2006 Elsevier B.V.保留所有权利。
The effect of the pineal indole hormone melatonin on the life span of mice, rats and fruit flies has been studied using various approaches. It has been observed that in female CBA, SHR, SAM and transgenic HER-2/neu mice long-term administration of melatonin was followed by an increase in the mean life span. In rats, melatonin treatment increased survival of male and female rats. In D. melanogaster, supplementation of melatonin to nutrient medium during developmental stages produced contradictory results, but and increase in the longevity of fruit flies has been observed when melatonin was added to food throughout the life span. In mice and rats, melatonin is a potent antioxidant both in vitro and in vivo. Melatonin alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at high concentration in the COMET assay. Melatonin has inhibited mutagenesis and clastogenic effect of a number of indirect chemical mutagens. Melatonin inhibits the development of spontaneous and 7-12-dimethlbenz(a)anthracene (DMBA)- or N-nitrosomethylurea-induced mammary carcinogenesis in rodents; colon carcinogenesis induced by 1,2-dimethylhydrazine in rats, N-diethyl nitrosamine-induced hepatocarcinogenesis in rats, DMBA-induced carcinogenesis of the uterine cervix and vagina in mice; benzo(a)pyrene-induced soft tissue carcinogenesis and lung carcinogenesis induced by urethan in mice. To identify molecular events regulated by melatonin, gene expression profiles were studied in the heart and brain of melatonin-treated CBA mice using cDNA gene expression arrays (15,247 and 16,897 cDNA clone sets, respectively). It was shown that genes controlling the cell cycle, cell/organism defense, protein expression and transport are the primary effectors for melatonin. Melatonin also increased the expression of some mitochondrial genes (16S, cytochrome c oxidases I and 3 (COX I and COX3), and NADH dehydrogenases I and 4 (ND1 and ND4)), which agrees with its ability to inhibit free radical processes. Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cu15, Dcamk11 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected. Thus, we believe that melatonin may be used for the prevention of premature aging and carcinogenesis. (c) 2006 Elsevier B.V. All rights reserved.