Inhibition of mTOR signaling protects photoreceptor cells against serum deprivation by reducing oxidative stress and inducing G2/M cell cycle arrest

Fan,Bin; Li,Fu‑Qaing; Song,Jing‑Yao; Chen,Xu; Li,Guang‑Yu

doi:10.3892/mmr.2016.5011

Inhibition of mTOR signaling protects photoreceptor cells against serum deprivation by reducing oxidative stress and inducing G2/M cell cycle arrest

Authors:
- Bin Fan
- Fu‑Qaing Li
- Jing‑Yao Song
- Xu Chen
- Guang‑Yu Li
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Affiliations: Department of Ophthalmology, Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Ophthalmology, Zhongshan Hospital of Fudan University, Shanghai 200032, P.R. China
Published online on: March 18, 2016 https://doi.org/10.3892/mmr.2016.5011
Pages: 3771-3778
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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