E3 ubiquitin ligase Triad1 promotes neuronal apoptosis by regulating the p53-caspase3 pathway after spinal cord injury

Abstract

Purpose

Spinal cord injury entails a high risk of major disability, but there is still no effective treatment for this condition. This study aims to explore the neuronal apoptosis after spinal cord injury, which is a key component of secondary injury processes, and plays a critical role in the development of neurological dysfunction.

Materials and Methods

We studied the expression of the E3 ubiquitin ligase Triad1 and its interaction with p53 in the spinal cord after a spinal cord contusion injury in rats. We explored the regulation function of Triad1 to the neuronal apoptosis through p53-caspase3 pathway in primary neurons.

Results

Triad1 was markedly up-regulated in the grey matter one day after injury, and the distribution and time point of Triad1 expression correlated with the presence of apoptotic neurons. Co-immunoprecipitation experiments further demonstrated that Triad1 interacted with p53 after spinal cord injury. Specific siRNA and overexpression plasmids for Triad1 were transfected into primary neurons, and the expression of both p53 and caspase3 was altered following the change of Triad1.

Conclusions

These findings indicate that Triad1 is involved in regulating the pathological process of neuronal apoptosis mediated by p53-caspase3 pathway after spinal cord injury.

Keywords:

• Spinal cord injury
• apoptosis
• interaction
• Triad1
• p53
• caspase3

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number: 81771319], Nantong Health and Family Planning Commission Research Project [grant number: WKZL2018001], Six Talent Peak Projects in Jiangsu Province [grant numbers: 2017-WSW-156], Nantong Science and Technology Plan Project [grant numbers: JC2019070, JC2020013, JC2020018], Medical research project of Jiangsu Commission of Health [grant numbers: ZDB2020004], Young Medical Talents Project of Jiangsu Province [grant numbers: QNRC2016413] and Nantong Social People's Livelihood Technology Project [grant numbers: MS12019027].