E2F1 Expression and Apoptosis Initiation in Crayfish and Rat Peripheral Neurons and Glial Cells after Axonal Injury

Abstract

Neurotrauma is among the main causes of human disability and mortality. The transcription factor E2F1 is one of the key proteins that determine the fate of cells. The involvement of E2F1 in the regulation of survival and death of peripheral nerve cells after axotomy has not been previously studied. We, for the first time, studied axotomy-induced changes in the expression and localization of E2F1 following axonal injury in rats and crayfish. Immunoblotting and immunofluorescence microscopy were used for the analysis of the expression and intracellular localization of E2F1 and its changes after axotomy. To evaluate whether this transcription factor promotes cell apoptosis, we examined the effect of pharmacological inhibition of E2F activity in axotomized rat models. In this work, axotomy caused increased expression of E2F1 as early as 4 h and even 1 h after axotomy of mechanoreceptor neurons and ganglia of crayfish ventral nerve cord (VNC), as well as rat dorsal root ganglia (DRG). The level of E2F1 expression increased both in the cytoplasm and the nuclei of neurons. Pharmacological inhibition of E2F demonstrated a pronounced neuroprotective activity against axotomized DRGs. E2F1 and downstream targets could be considered promising molecular targets for the development of potential neuroprotective agents.

The Role of Hydrogen Sulfide in the Localization and Expression of p53 and Cell Death in the Nervous Tissue in Traumatic Brain Injury and Axotomy

“…Since axotomy does not cause DNA damage, potential signals for p53 synthesis include transcription factors such as E2F1, c-Myc, p38, as well as the universal second messenger H 2 S. An increase in the level of these proteins was found in axotomized VNC ganglia [52]. In a recent study, we found an increase in the expression of E2F1 in MRN, VNC of crayfish, as well as ganglia of the dorsal roots of the spinal cord during axotomy [53]. It has been shown that H 2 S can regulate the expression of E2F1 [54].…”

Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation

“…The radiation-induced neuropathy of the sciatic nerve has reported the presence of tissue apoptosis and confirmed dysregulation of Bcl-2 and Bax expression in sciatic nerve tissue [ 173 , 174 , 175 ]. In addition, the cisplatin-resistant ovarian cancer cell line model also exhibited apoptosis via intrinsic and extrinsic mechanisms incorporating p53 alterations [ 176 ].…”