Research Paper Volume 12, Issue 13 pp 13594—13617

The transcription factor CREB acts as an important regulator mediating oxidative stress-induced apoptosis by suppressing αB-crystallin expression

Ling Wang1, *, , Qian Nie1, *, , Meng Gao2,3, *, , Lan Yang1, *, , Jia-Wen Xiang1,4, *, , Yuan Xiao1, , Fang-Yuan Liu1, , Xiao-Dong Gong1, , Jia-Ling Fu1, , Yan Wang1, , Quan Dong Nguyen4, , Yizhi Liu1, , Mugen Liu2, , David Wan-Cheng Li1, ,

  • 1 The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510230, Guangdong, China
  • 2 Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China
  • 3 Medical College, Henan University of Science and Technology, Luoyang 471000, Henan, China
  • 4 Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA 94303, USA
* Equal contribution

Received: February 1, 2020       Accepted: May 3, 2020       Published: June 17, 2020
How to Cite

Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The general transcription factor, CREB has been shown to play an essential role in promoting cell proliferation, neuronal survival and synaptic plasticity in the nervous system. However, its function in stress response remains to be elusive. In the present study, we demonstrated that CREB plays a major role in mediating stress response. In both rat lens organ culture and mouse lens epithelial cells (MLECs), CREB promotes oxidative stress-induced apoptosis. To confirm that CREB is a major player mediating the above stress response, we established stable lines of MLECs stably expressing CREB and found that they are also very sensitive to oxidative stress-induced apoptosis. To define the underlying mechanism, RNAseq analysis was conducted. It was found that CREB significantly suppressed expression of the αB-crystallin gene to sensitize CREB-expressing cells undergoing oxidative stress-induced apoptosis. CREB knockdown via CRISPR/CAS9 technology led to upregulation of αB-crystallin and enhanced resistance against oxidative stress-induced apoptosis. Moreover, overexpression of exogenous human αB-crystallin can restore the resistance against oxidative stress-induced apoptosis. Finally, we provided first evidence that CREB directly regulates αB-crystallin gene. Together, our results demonstrate that CREB is an important transcription factor mediating stress response, and it promotes oxidative stress-induced apoptosis by suppressing αB-crystallin expression.


BDGF: brain-derived neurotrophic factor; CREB: cAMP response element binding protein; EGFP: enhanced green fluorescence protein; αB: αB-crystallin; EGFP-αB: enhanced green fluorescence and αB-crystallin fusion protein; DMEM: Dulbecco's modified eagle medium; GO: glucose oxidase; NGF: nerve growth factor; OS: oxidative Stress; PAGE: polyacrylamide gel electrophoresis; PBS: phosphate-buffered saline; αTN4-1: mouse lens epithelial cells; SDS: sodium dodecylsulfate; TBS: tris-buffered saline; TBS-T: tris-buffered saline with tween-20.