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

Lei Wang1, Li Zhang2, Billy K C Chow3

  • 1School of Life Sciences, Guangzhou University, Guangzhou, China.

Journal of Molecular Neuroscience : MN
|March 16, 2019
PubMed

Insights

Secretin (SCT) protects developing neurons by increasing anti-apoptotic proteins Bcl-2 and Bcl-xL. This neuroprotective effect is mediated by the CREB pathway, involving cAMP/PKA and MAPK/ERK signaling.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Secretin (SCT) plays a role in physiological processes and is linked to preventing apoptosis in developing brains.
  • The molecular mechanisms behind SCT's neuroprotective effects are not well understood.
  • Bcl-2 family proteins, including Bcl-2 and Bcl-xL, are critical regulators of neuronal apoptosis.

Purpose of the Study:

  • To elucidate the molecular mechanism of secretin's neuroprotective effects during brain development.
  • To investigate the role of Bcl-2 family proteins in SCT-mediated neuronal survival.
  • To identify the signaling pathways involved in SCT-induced anti-apoptotic gene expression.

Main Methods:

  • Analysis of Bcl-2 and Bcl-xL transcript levels in SCT knockout mice and ex vivo cerebellar slices.
  • Treatment of cerebellar slices with SCT and assessment of Bcl-2 and Bcl-xL expression.
  • Investigation of the involvement of CREB, cAMP/PKA, and MAPK/ERK signaling pathways.

Main Results:

  • SCT knockout mice showed reduced Bcl-2 and Bcl-xL transcript levels in the developing cerebellum.
  • SCT treatment increased Bcl-2 and Bcl-xL expression in a time-dependent manner.
  • SCT-induced Bcl-2 and Bcl-xL upregulation was dependent on CREB phosphorylation, mediated by cAMP/PKA and MAPK/ERK cascades.

Conclusions:

  • Secretin promotes neuronal survival by upregulating anti-apoptotic proteins Bcl-2 and Bcl-xL.
  • A novel signaling cascade involving SCT, cAMP/PKA, MAPK/ERK, and CREB mediates neuroprotection.
  • These findings reveal a previously uncharacterized mechanism for SCT in regulating the intrinsic apoptosis pathway.
Keywords:
ApoptosisBcl-2 family proteinsCREBERK1/2PKASecretin

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