The inhibitory effect of minocycline on radiation-induced neuronal apoptosis via AMPKα1 signaling-mediated autophagy.
The inhibitory effect of minocycline on radiation-induced neuronal apoptosis via AMPKα1 signaling-mediated autophagy.
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米诺环素通过 AMPK α1 信号介导的自噬对辐射诱导的神经元凋亡的抑制作用
DOI：
10.1038/s41598-017-16693-8
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发表时间：
2017-11-27
影响因子：
4.6
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Zhang L;Huang P;Chen H;Tan W;Lu J;Liu W;Wang J;Zhang S;Zhu W;Cao J;Tian Y;Yang H
由于人们越来越关注接受放射治疗的脑肿瘤患者的辐射引起的认知障碍，制定和评估对策已成为不可避免的。我们之前的研究发现，二甲胺四环素是一种临床可用的抗生素，可以很容易地穿过血脑屏障，减轻辐射引起的大鼠长期记忆丧失，并伴有海马神经元凋亡减少。因此，在本研究中，我们报告了米诺环素神经保护作用的未知机制。我们在体外证明二甲胺四环素可以阻止原代神经元的辐射诱导凋亡，并促进辐射诱导的自噬。此外，通过永活小鼠海马神经元细胞系HT22细胞，我们发现二甲胺四环素对辐照HT22细胞的保护作用与DNA损伤修复无关，因为二甲胺四环素不促进辐照HT22细胞DNA DSB的修复。进一步研究表明，二甲胺四环素显著增强x照射诱导的AMPKα1活化和自噬，从而减少细胞凋亡。此外，尽管米诺环素的抗氧化潜能可能参与了其抑制细胞凋亡的作用，但它并没有参与其对辐射诱导的ampk α1介导的自噬的增强作用。综上所述，我们揭示了二甲胺四环素对辐照神经元保护作用的新机制，例如二甲胺四环素通过增强辐射诱导的ampk α1介导的自噬来保护神经元免受辐射诱导的凋亡。
Due to an increasing concern about radiation-induced cognitive deficits for brain tumor patients receiving radiation therapy, developing and evaluating countermeasures has become inevitable. Our previous study has found that minocycline, a clinical available antibiotics that can easily cross the blood brain barrier, mitigates radiation-induced long-term memory loss in rats, accompanied by decreased hippocampal neuron apoptosis. Thus, in the present study, we report an unknown mechanism underlying the neuroprotective effect of minocycline. We demonstrated that minocycline prevented primary neurons from radiation-induced apoptosis and promoted radiation-induced autophagy in vitro. Moreover, using an immortalized mouse hippocampal neuronal cell line, HT22 cells, we found that the protective effect of minocycline on irradiated HT22 cells was not related to DNA damage repair since minocycline did not facilitate DNA DSB repair in irradiated HT22 cells. Further investigation showed that minocycline significantly enhanced X-irradiation-induced AMPKα1 activation and autophagy, thus resulting in decreased apoptosis. Additionally, although the antioxidant potential of minocycline might contribute to its apoptosis-inhibitory effect, it was not involved in its enhancive effect on radiation-induced AMPKα1-mediated autophagy. Taken together, we have revealed a novel mechanism for the protective effect of minocycline on irradiated neurons, e.g. minocycline protects neurons from radiation-induced apoptosis via enhancing radiation-induced AMPKα1-mediated autophagy.
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影响因子：
4.1
作者：
Cochran DC;Chan MD;Aklilu M;Lovato JF;Alphonse NK;Bourland JD;Urbanic JJ;McMullen KP;Shaw EG;Tatter SB;Ellis TL
通讯作者：
Ellis TL
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
82.9
作者：
Chen, M;Ona, VO;Friedlander, RM
通讯作者：
Friedlander, RM
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1158/1078-0432.ccr-11-2903
发表时间：
2013-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Greene-Schloesser D;Moore E;Robbins ME
通讯作者：
Robbins ME