NO-Dependent Mechanisms of p53 Expression and Cell Death in Rat’s Dorsal Root Ganglia after Sciatic-Nerve Transection

• Published in: Biomedicines 2022-07, Vol.10 (7), p.1664
• Main Authors: Rodkin, Stanislav, Dzreyan, Valentina, Bibov, Mikhail, Ermakov, Alexey, Derezina, Tatyana, Kirichenko, Evgeniya
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Axotomy; Cell cycle; Cell death; Cytoplasm; Dorsal root ganglia; dorsal root ganglion; Glial cells; inducible NO-synthase; Microscopy; Neuronal-glial interactions; Neurons; Neuroprotection; nitric oxide; Nitric-oxide synthase; p53; Physiology; Proteins; Spinal cord; Trauma
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10071664

Peripheral-nerve injury is a frequent cause of disability. Presently, no clinically effective neuroprotectors have been found. We have studied the NO-dependent expression of p53 in the neurons and glial cells of the dorsal root ganglia (DRG) of a rat’s spinal cord, as well as the role of NO in the death of these cells under the conditions of axonal stress, using sciatic-nerve axotomy as a model. It was found out that axotomy led to the nuclear–cytoplasmic redistribution of p53 in neurons, 24 h after trauma. The NO donor led to a considerable increase in the level of p53 in nuclei and, to a smaller degree, in the cytoplasm of neurons and karyoplasm of glial cells 4 and 24 h after axotomy. Application of a selective inhibitor of inducible NO-synthase (iNOS) provided the opposite effect. Introduction of the NO donor resulted in a significant increase in cell death in the injured ipsilateral DRG, 24 h and 7 days after trauma. The selective inhibitor of iNOS demonstrated a neuroprotective effect. Axotomy was shown to upregulate the iNOS in nuclei and cytoplasm of DRG cells. The NO-dependent expression of p53, which is particularly achieved through iNOS activation, is believed to be a putative signaling mechanism of neural and glial-cell death after axotomy.