Manganese superoxide dismutase: beyond life and death.
Manganese superoxide dismutase: beyond life and death.
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DOI：
10.1007/s00726-010-0600-9
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发表时间：
2012-01
期刊：
影响因子：
3.5
通讯作者：
St Clair, Daret K.
中科院分区：
文献类型：
--
作者：
Holley, Aaron K.;Dhar, Sanjit Kumar;Xu, Yong;St Clair, Daret K.
锰超氧化物歧化酶（MnSOD）是一种定位于线粒体的核编码抗氧化酶。MnSOD的表达对有氧生物的生存至关重要。在人类MnSOD启动子控制下表达荧光素酶报告基因的转基因小鼠表明，MnSOD水平在癌症形成之前降低。在DMBA/TPA皮肤癌变模型中，转基因小鼠中MnSOD的过表达降低了乳头状瘤的发生率和多样性。然而，MnSOD缺乏并不会导致类似处理的皮肤组织的致瘤性增强，因为MnSOD可以调节p53介导的细胞凋亡和ap -1介导的细胞增殖途径。细胞凋亡与线粒体p53水平的增加有关，这表明MnSOD缺乏与线粒体介导的细胞凋亡之间存在联系。p53的激活可以通过应用SOD模拟物（MnTE-2-PyP5+）来预防。因此，p53易位到线粒体和随后的MnSOD失活解释了观察到的线粒体功能障碍，导致p53诱导的细胞凋亡的转录依赖机制。在细胞凋亡后但在细胞增殖之前给药MnTE-2-PyP5+会抑制蛋白羰基，降低AP-1的活性和增殖细胞核抗原的水平，而不降低TPA治疗后p53的活性或DNA片段化。值得注意的是，在细胞增殖之前接受MnTE-2-PyP5+的小鼠中，皮肤肿瘤的发生率和多样性急剧降低。这些结果表明，MnSOD的作用超出了其对生存的重要作用，并提出了一种抗氧化方法用于癌症干预的新策略。
Manganese superoxide dismutase (MnSOD) is a nuclear-encoded antioxidant enzyme that localizes to the mitochondria. Expression of MnSOD is essential for the survival of aerobic life. Transgenic mice expressing a luciferase reporter gene under the control of the human MnSOD promoter demonstrate that the level of MnSOD is reduced prior to the formation of cancer. Overexpression of MnSOD in transgenic mice reduces the incidences and multiplicity of papillomas in a DMBA/TPA skin carcinogenesis model. However, MnSOD deficiency does not lead to enhanced tumorigenicity of skin tissue similarly treated because MnSOD can modulate both the p53-mediated apoptosis and AP-1-mediated cell proliferation pathways. Apoptosis is associated with an increase in mitochondrial levels of p53 suggesting a link between MnSOD deficiency and mitochondrial-mediated apoptosis. Activation of p53 is preventable by application of a SOD mimetic (MnTE-2-PyP5+). Thus, p53 translocation to mitochondria and subsequent inactivation of MnSOD explain the observed mitochondrial dysfunction that leads to transcription-dependent mechanisms of p53-induced apoptosis. Administration of MnTE-2-PyP5+ following apoptosis but prior to proliferation leads to suppression of protein carbonyls and reduces the activity of AP-1 and the level of the proliferating cellular nuclear antigen, without reducing the activity of p53 or DNA fragmentation following TPA treatment. Remarkably, the incidence and multiplicity of skin tumors are drastically reduced in mice that receive MnTE-2-PyP5+ prior to cell proliferation. The results demonstrate the role of MnSOD beyond its essential role for survival and suggest a novel strategy for an antioxidant approach to cancer intervention.
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影响因子：
64.5
作者：
BORGSTAHL, GEO;PARGE, HE;TAINER, JA
通讯作者：
TAINER, JA
DOI：
10.1016/j.bbrc.2008.04.022
发表时间：
2008-06-13
影响因子：
3.1
作者：
Chen, Che-Sheng;Zhao, Qing;Wu, Wu-Tong
通讯作者：
Wu, Wu-Tong
影响因子：
11.2
作者：
Chen, DX;Yu, ZY;Lopez, CD
通讯作者：
Lopez, CD
影响因子：
14.9
作者：
Buzek, J;Latonen, L;Laiho, M
通讯作者：
Laiho, M
影响因子：
3.3
作者：
Batinic-Haberle, Ines;Benov, Ludmil T.
通讯作者：
Benov, Ludmil T.