Pentazocine Protects SN4741 Cells Against MPP+-Induced Cell Damage via Up-Regulation of the Canonical Wnt/β-Catenin Signaling Pathway

Abstract

The Wnt/β-catenin signaling pathway has been linked to many neurodegenerative diseases including Parkinson’s disease (PD). A glycoprotein named Dickkopf-1 (Dkk1) can combine with the receptor complex on cell membrane to inhibit Wnt/β-catenin signaling. Opioids, a series of compounds including morphine, fentanyl and pentazocine, have been reported to contribute to the up-regulation of Wnt/β-catenin signaling. Naloxone is an antagonist that has been used as an antidote to opioids through mu-opioid receptor. 1-methyl-4-phenylpyridinium (MPP+), which serves as a selective toxin for dopaminergic neurons, has been used to create experimental models of PD. In our study, we examined the protective effects of pentazocine against MPP+-induced cell death in the nigral dopaminergic cell line, SN4741 and tried to elucidate the molecular mechanisms underlying such protective effects. The data showed that pretreatment with pentazocine significantly rescued the SN4741 cell against MPP+. Moreover, the MPP+-exposed SN4741 cells exhibited a down-regulation of β-catenin, which could be restored by treatment with pentazocine. However, Dkk1 but not naloxonewas associated with the abrogation of protective effect of pentazocine. These results suggest that pentazocine alleviates MPP+-induced SN4741 cells apoptosis via the up-regulation of canonical Wnt/β-catenin signaling.

Wnt/β-Catenin Signaling Pathway Governs a Full Program for Dopaminergic Neuron Survival, Neurorescue and Regeneration in the MPTP Mouse Model of Parkinson’s Disease

“…Amongst others GSK-3β inhibitors, bromoinduru-30-oxime (6-BIO) was shown to protect hippocampal neurons from the apoptotic effects of amyloid-β (Aβ) oligomers via direct activation of the Wnt/β-catenin pathway [154]. Interestingly enough, different classes of pharmacological agents including statins (simvastin) [87], opioids (pentazocine) [88], nicotinic receptor modulators [89], or derivatives of natural products and immunomodulators [84,86,90,91,155,156], amongst others, were reported to protect mDAergic neurons against apoptosis, in either in vivo or in vitro models of PD, via the activation of the Wnt/β-catenin signaling pathway, thus supporting the critical role of this signaling system for the protection of mDAergic neurons against cytotoxicity.…”

“…The growing field of Wnt signaling in neurodegeneration and regeneration was highlighted in a Special Issue “Wnt signaling cascades in neurodevelopment, neurodegeneration, and regeneration”, featuring the progresses achieved and the future challenges in the field [81]. So far, a wide panel of genetic, physiopathological, or neurotoxic conditions affecting mDA neurons in PD were shown to strongly impair canonical Wnt/β-catenin signaling, while an increasing number of pharmacological and immunomodulatory agents affording neuroprotection were recognized to activate the canonical Wnt/β-catenin signaling pathway, promoting neuroprotection and immunomodulation, and counteracting the impairment of neurogenesis in PD injured brain (Figure 2) [49,50,51,52,53,54,55,56,57,82,83,84,85,86,87,88,89,90,91].…”

Impact of Glucocorticoid on a Cellular Model of Parkinson’s Disease: Oxidative Stress and Mitochondrial Function

“…On the basis of these observations, we decided to research the interplay of CORT and MPP + in dopaminergic neuronal cell cultures as a potential model of PD pathology and mild to moderate emotional stress. We applied a well-established in vitro model of PD induced by the administration of the neurotoxin MPP + [40,41] and combined it with the administration of CORT [24,42].…”

Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson's disease

“…Amongst others GSK-3β inhibitors, bromoinduru-30-oxime-(6-BIO) was shown to protect hippocampal neurons from the apoptotic effects of amyloid-β (Aβ) oligomers via a direct activation of Wnt/β-catenin pathway [ 320 ]. Interestingly enough, different classes of pharmacological agents including statins (simvastin) [ 321 ], opioids [ 322 ], nicotinic receptor modulators [ 323 ], were reported to protect neuronal cells, including mDAns, against apoptosis, in either in vivo or in vitro models of PD, via the activation of Wnt/β-catenin signaling pathway, thus supporting the critical role of this signaling system for the protection of mDAergic neurons against cytotoxicity.…”