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Secretin Prevents Apoptosis in the Developing Cerebellum Through Bcl-2 and Bcl-xL

  • Lei Wang
  • Li ZhangEmail author
  • Billy K. C. ChowEmail author
Article

Abstract

Secretin (SCT) is involved in a variety of physiological processes and has been implicated in preventing apoptosis during brain development. However, little is known about the molecular mechanism underlying its neuroprotective effects. The B cell lymphoma 2 (Bcl-2) family proteins, such as Bcl-2 and Bcl-xL, determine the commitment of neurons to apoptosis. In SCT knockout mice, we found reduced transcript levels of anti-apoptotic genes Bcl-2 and Bcl-xL, but not of pro-apoptotic gene Bax, in the developing cerebellum. SCT treatment on ex vivo cultured cerebellar slices triggered a time-dependent increase of Bcl-2 and Bcl-xL expression. This SCT-induced transcriptional regulation of Bcl-2 and Bcl-xL was dependent on the cyclic AMP (cAMP) response element-binding protein (CREB), which is a key survival factor at the convergence of multiple signaling cascades. We further demonstrated that activation of CREB by SCT was mediated by cAMP/protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) cascades. These findings, collectively, provide an uncharacterized signaling cascade for SCT-mediated neuronal survival, in which SCT promotes the key anti-apoptotic elements Bcl-2 and Bcl-xL in the intrinsic death pathway through PKA- and ERK-regulated CREB phosphorylation.

Keywords

Secretin Apoptosis Bcl-2 family proteins CREB PKA ERK1/2 

Notes

Funding Information

This work is supported by Hong Kong Research Grant Council grant GRF 765113M to Professor B.K.C. Chow, and National Natural Science Foundation of China (#31500842) to Dr. L. Zhang.

Compliance with Ethical Standards

All animal experiments were conducted according to the protocols approved by Committee on the Use of Living Animals in Teaching and Research at the University of Hong Kong.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Life SciencesGuangzhou UniversityGuangzhouChina
  2. 2.GHM Institute for CNS RegenerationJinan UniversityGuangzhouChina
  3. 3.School of Biological SciencesThe University of Hong KongHong KongHong Kong

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