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Pin1 Is Regulated by CaMKII Activation in Glutamate-Induced Retinal Neuronal Regulated Necrosis

Shuchao Wang1,2, Lvshuang Liao1, Yanxia Huang1

  • 1Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.

Frontiers in Cellular Neuroscience
|July 12, 2019
PubMed

Insights

Calcium/calmodulin-dependent protein kinase II (CaMKII) activates peptidyl-prolyl isomerase 1 (Pin1), driving glutamate-induced regulated necrosis (RN) in retinal neurons. Inhibiting CaMKII protects against neuronal death and restores visual function.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Ophthalmology

Background:

  • Previous research identified peptidyl-prolyl isomerase 1 (Pin1)-modulated regulated necrosis (RN) in retinal neurons post-glutamate injury.
  • Glutamate excitotoxicity is a key factor in retinal neurodegeneration.

Purpose of the Study:

  • To investigate the role of calcium/calmodulin-dependent protein kinase II (CaMKII) in Pin1-modulated RN.
  • To explore CaMKII as a potential therapeutic target for glutamate-induced retinal injury.

Main Methods:

  • Utilized cultured rat retinal neurons and an in vivo animal model.
  • Administered glutamate to induce excitotoxicity and observed neuronal responses.
  • Employed KN-93, a specific CaMKII inhibitor, to assess its protective effects.
  • Performed flash electroretinograms to evaluate visual function recovery.

Main Results:

  • Glutamate overload, primarily via ionotropic glutamate receptors, activates CaMKII.
  • Activated CaMKII leads to Pin1 activation and subsequent RN.
  • Inhibition of CaMKII with KN-93 significantly reduced glutamate-induced RN in vitro and in vivo.
  • CaMKII inhibition facilitated recovery of visual function impaired by glutamate.

Conclusions:

  • CaMKII acts as an up-regulator of Pin1, mediating glutamate-induced RN in retinal neurons.
  • This pathway represents a complementary mechanism for Pin1 activation in necrosis.
  • CaMKII inhibition offers a promising therapeutic strategy for neurodegenerative diseases affecting the retina and CNS.
Keywords:
CaMKIIPin1calciumglutamateregulated necrosis

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