Inhibition of mTOR signaling protects photoreceptor cells against serum deprivation by reducing oxidative stress and inducing G2/M cell cycle arrest.
Inhibition of mTOR signaling protects photoreceptor cells against serum deprivation by reducing oxidative stress and inducing G2/M cell cycle arrest.
复制标题
mTOR 信号传导的抑制可通过减少氧化应激和诱导 G2/M 细胞周期停滞来保护感光细胞免受血清剥夺的影响。
DOI：
10.3892/mmr.2016.5011
复制
发表时间：
2016-05
影响因子：
3.4
通讯作者：
Li GY
中科院分区：
文献类型：
--
作者：
Fan B;Li FQ;Song JY;Chen X;Li GY
哺乳动物雷帕霉素靶点（mTOR）通路是一个重要的细胞信号中枢，它整合内部和外部信号来调节细胞周期、蛋白质合成和代谢。本研究假设抑制mTOR信号可能会诱导细胞进入更低和更稳定的生物能量状态，在这种状态下神经元对各种损伤具有更大的抵抗力。利用血清剥夺模拟光感受器细胞（661W细胞）的神经营养因子戒断，并研究mTOR通路抑制后的神经保护机制。用mTOR特异性抑制剂雷帕霉素治疗，可降低细胞内活性氧水平，抑制氧化应激，减轻线粒体功能障碍。此外，抑制mTOR信号传导诱导G2/M细胞周期阻滞，从而提供修复受损DNA和阻断细胞死亡级联的机会。这些结果表明，抑制mTOR对血清缺失的661W细胞具有神经保护作用。综上所述，mTOR通路是细胞周期调控和能量代谢的关键分子信号，抑制mTOR通路可减轻神经营养因子戒断性损伤。这些观察结果可能为视网膜退行性疾病的治疗提供证据，因为通过阻断mTOR信号传导诱导神经元进入更低和更稳定的生物能量状态可能会减缓神经退行性疾病的进展。
The mammalian target of rapamycin (mTOR) pathway is a crucial cellular signaling hub, which integrates internal and external cues to modulate the cell cycle, protein synthesis and metabolism. The present study hypothesized that inhibiting mTOR signaling may induce cells to enter lower and more stable bioenergetic states, in which neurons have greater resistance to various insults. Neurotrophin withdrawal from photoreceptor cells (661W cells) was mimicked using serum deprivation, and the neuroprotective mechanisms were studied following suppression of the mTOR pathway. Treatment with an mTOR specific inhibitor, rapamycin, reduced intracellular levels of reactive oxygen species, suppressed oxidative stress, and attenuated mitochondrial dysfunction. In addition, inhibiting mTOR signaling induced a G2/M cell cycle arrest, thus providing an opportunity to repair damaged DNA and block the cell death cascade. These results suggested that inhibition of mTOR had a neuroprotective effect on serum-deprived 661W cells. In conclusion, the mTOR pathway is a critical molecular signal for cell cycle regulation and energy metabolism, and inhibiting the mTOR pathway may attenuate neurotrophin withdrawal-induced damage. These observations may provide evidence for the treatment of retinal degenerative disease, since inducing neurons into a lower and more stable bioenergetic state by blocking mTOR signaling may slow the progression of neurodegenerative diseases.