Protective Role of UCP2 in Oxidative Stress and Apoptosis during the Silent Phase of an Experimental Model of Epilepsy Induced by Pilocarpine

Abstract

Neuroprotection is a desirable process in many neurological disorders, yet complex mechanisms involved in this field are not completely understood. The pilocarpine epilepsy model causes potent, seizure-induced excitotoxicity cell death and mitochondria impairment. The present study is aimed at investigating the role of UCP2, a ROS negative regulator, in the neuroprotection after cholinergic insult. Our data demonstrated that UCP2 expression was augmented in the rat hippocampus 3 days after status epilepticus (SE), reaching a peak on the fifth day, then returning to basal levels. Concomitantly, phospho-AKT expression levels were higher in the hippocampus during the early silent phase (5 days after SE). Additionally, it was demonstrated that the blockade of UCP2 by antisense oligonucleotides (ASO) in SE rats successfully diminished both UCP2 mRNA and protein contents. SE ASO rats presented increased mitochondrial proapoptotic factor expression, caspase-3 activity, inflammatory cytokine expression, and ROS formation. Moreover, ASO treatment diminished p-AKT expression and antioxidant enzyme activities after pilocarpine insult. In conclusion, the present results highlight the neuroprotective actions of UCP2, acting in the inhibition of apoptotic factors and oxidative stress, to increase neuron survival after SE onset.

Differential transcriptome response to proton versus X-ray radiation reveals novel candidate targets for combinatorial PT therapy in lymphoma

“…Interestingly, the GO gene set "mitochondrial transport" identified PT specific repression of two genes UCP2 and MGARP (Fig4C). Expression of UCP2 has been directly linked to ROS levels 32,33 , and MGARP has been implicated in mitochondrial polarization and trafficking 34,35 . UCP2 and MGARP repression by PT was validated by RT-qPCR in BL41 and RAMOS cells (Fig4D).…”

“…Moreover, a database screen revealed that 23 known PPARG target genes are a part of the PT transcriptome signature in lymphoma cells. Inhibition of PPARG in combination with PT led to decreased expression of two genes UCP2 and HSP90AA1 which are implicated in protein folding 69 and apoptosis control 32,33 . Both drugs also showed cytotoxicity against lymphoma cells in the absence of PT, a finding which demonstrates potential value of PPARg inhibition for clinical treatment.…”

Deletion of mitochondrial uncoupling protein 2 exacerbates mitophagy and cell apoptosis after cerebral ischemia and reperfusion injury in mice

“…Several studies have shown that UCP2 plays important roles in regulating oxidative stress and mitochondrial apoptosis signaling. Abundant evidence also demonstrated that UCP2 plays a significant role in the pathogenesis of cerebral ischemia/reperfusion (I/R) damage [3,4,5]. Our previous studies have shown that deletion of UCP2 gene increases infarct volume after ischemic stroke;…”

Rh-CSF1 Attenuates Oxidative Stress and Neuronal Apoptosis via the CSF1R/PLCG2/PKA/UCP2 Signaling Pathway in a Rat Model of Neonatal HIE

“…Mo et al showed that PKA exerted an antiapoptotic role by activating UCP2 after subarachnoid hemorrhage [ 40 ]. UCP2 can provide an important effect in attenuating mitochondrial ROS levels and cell death [ 67 , 68 ]. Increased expression or activation of UCP2 could suppress neuronal damage induced by OS in CNS diseases, such as epilepsy, stroke, and subarachnoid hemorrhage [ 36 , 37 , 58 ].…”