MiR-137-3p rescue motoneuron death by targeting calpain-2

Nitric Oxide. 2018 Apr 1:74:74-85. doi: 10.1016/j.niox.2018.01.008.

Abstract

Brachial plexus root avulsion (BPRA) is a type of injury that leads to motor function loss as a result of motoneurons (MNs) degeneration. Here we identified that the reduced expression of rat miR-137-3p in the ventral horn of spinal cord was associated with MNs death. However, the pathophysiological role of miR-137-3p in root avulsion remains poorly understood. We demonstrated that the calcium-activated neutral protease-2 (calpain-2) was a direct target gene of miR-137-3p with miR-137-3p binding to the 3'-untranslated region of calpain-2. Silencing of calpain-2 suppressed the expression of neuronal nitric oxide synthase (nNOS), a primary source of nitric oxide (NO). After avulsion 2 weeks, up-regulation of miR-137-3p in the spinal cord reduced calpain-2 levels and nNOS expression inside spinal MNs, resulting in an amelioration of the MNs death. These events provide new insight into the mechanism by which upregulation of miR-137-3p can impair MN survival in the BPRA.

Keywords: Brachial plexus root avulsion; Calpain-2; Neuron death; miR-137–3p; nNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brachial Plexus / injuries
  • Brachial Plexus / metabolism
  • Calpain / genetics*
  • Cell Death
  • Cells, Cultured
  • HEK293 Cells
  • Humans
  • Injections, Intraperitoneal
  • MicroRNAs / genetics*
  • MicroRNAs / pharmacology
  • Motor Neurons / cytology*
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / metabolism
  • PC12 Cells
  • Rats

Substances

  • MIRN137 microRNA, rat
  • MicroRNAs
  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Calpain
  • Capn2 protein, rat