SUMO-1 delays neuronal damage in the spinal cord following ischemia/reperfusion

Mol Med Rep. 2017 Jun;15(6):4312-4318. doi: 10.3892/mmr.2017.6527. Epub 2017 Apr 28.

Abstract

The present study investigated the protective effects of small ubiquitin-like modifier 1 (SUMO-1) on spinal cord ischemic damage in rabbits. A trans‑activator of transcription (Tat)‑SUMO‑1 fusion protein was prepared, and transient spinal cord ischemia was induced by occlusion of the abdominal aorta for 15 min. Vehicle (glycerol) or 1 mg/kg Tat-1-SUMO‑1 was administered intraperitoneally to the rabbits immediately following ischemia/reperfusion. Administration of Tat-SUMO-1 did not lead to significant alterations in arterial blood gases [partial pressure (Pa)CO2 and PaO2], pH, or blood glucose levels prior to ischemia, 10 min after occlusion or 10 min after reperfusion. Mean arterial pressure was significantly decreased only during occlusion. Motor behaviors were assessed at 24, 48 and 72 h after ischemia/reperfusion using Tarlov's criteria. Administration of Tat‑SUMO‑1 significantly improved Tarlov scores 24 h after ischemia/reperfusion and the number of cresyl violet positive neurons was significantly increased in the ventral horn of the spinal cord compared with the vehicle‑treated group. However, Tarlov scores were consistently decreased at 48 and 72 h after ischemia/reperfusion in the Tat‑SUMO‑1‑treated group, and Tarlov scores and the number of cresyl violet positive neurons were not significantly different between the vehicle‑ and Tat‑SUMO‑1‑treated groups after 72 h. Tat-SUMO‑1 administration significantly ameliorated a reduction in Cu, Zn‑superoxide dismutase activity and an increase in lipid peroxidation 24 h after ischemia/reperfusion; however, these effects were not present at 72 h. These results suggested that Tat‑SUMO‑1 may delay, although not protect against, neuronal death by regulating oxidative stress in the ventral horn of the spinal cord and that combination therapy using Tat‑SUMO‑1 with other compounds may provide a therapeutic approach to decrease neuronal damage.

MeSH terms

  • Animals
  • Gene Products, tat / metabolism
  • Gene Products, tat / pharmacology
  • Lipid Peroxidation / drug effects
  • Male
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Rabbits
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • SUMO-1 Protein / metabolism
  • SUMO-1 Protein / pharmacology*
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Spinal Cord Ischemia / drug therapy*
  • Spinal Cord Ischemia / metabolism

Substances

  • Gene Products, tat
  • Neuroprotective Agents
  • SUMO-1 Protein