Role of JNK and Involvement of p53 in Stimulation of Growth Potential Realization of Mesenchymal Precursor Cells by Alkaloid Songorine

Zyuz’kov, G. N.; Zhdanov, V. V.; Удут, Е. В.; Мирошниченко, Л. А.; Chaikovskii, A. V.; Симанина, Е. В.; Удут, В. В.; Ставрова, Л. А.; Polyakova, T. Yu.; Minakova, M. Yu.; Trifonova, O. Yu.; Gridneva, T. D.; Дыгай, А. М.

doi:10.1007/s10517-015-3099-y

Cited by 9 publications

(3 citation statements)

References 15 publications

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“…p53 is reported to regulate neurite growth and axon regeneration (Di Giovanni 2006). JNK signaling activates p53 signaling (Zyuz'kov et al 2015, Akhter et al 2015. It is reported that JNK/p53 signaling is involved in AD pathogenesis (Shi et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin ameliorates cognitive impairment in Parkinson’s disease via JNK/p53 signaling

Huan

Wang

et al. 2022

Metab Brain Dis

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Paeoniflorin (PF) has numerous benefits, including anti-inflammatory and anti-apoptosis effects. However, it is not clear if it has neuroprotective effects against cognitive impairment (CI) in Parkinson’s disease (PD). Through network pharmacology, we identified probable targets as well as signal pathways through which PF might affect CI in PD. Then, we experimentally validated our findings. The core genes of the protein-protein interactions (PPI) network include MAPK8 (JNK), TP53, CASP3 (caspase-3), postsynaptic density protein-95 (PSD-95) and synaptophysin (SYN). Pathway enrichment analysis revealed that genes involved in apoptosis and mitogen-activated protein kinase (MAPK) signaling were significantly enriched. Because JNK is a key mediator of p53-induced apoptosis, we wondered if JNK/p53 pathway influences the effects of PF against apoptosis in mouse model of PD. Molecular docking analysis showed that PF had good affinity for JNK/p53. The results of the experiments indicated that PF ameliorated behavioral impairments and upregulated the expression of the dopamine (DA) neurons, suppressed cell apoptosis in substantia nigra pars compacta (SNpc) of PD. Additionally, PF improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury by inhibiting apoptosis in hippocampal neurons of the CA1 and CA3, and upregulating PSD-95 as well as SYN protein levels. Similar protective effects were observed upon JNK/p53 pathway inhibition using SP600125. Overall, PF improved CI in PD by inhibiting JNK/p53 pathway.

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Section: Discussionmentioning

confidence: 99%

Paeoniflorin ameliorates cognitive impairment in Parkinson’s disease via JNK/p53 signaling

Huan

Wang

et al. 2022

Metab Brain Dis

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show abstract

“…p53 is reported to regulate neurite growth and axon regeneration (Di et al, 2006). JNK signaling activates p53 signaling (Zyuz'kov et al, 2015, Akhter et al, 2015. It is reported that JNK/p53 signaling is involved in AD pathogenesis (Shi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin Ameliorates Cognitive Impairment in Parkinson’s Disease via JNK/p53 Signaling

Huan

Wang

et al. 2021

Preprint

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Paeoniflorin (PF) has numerous benefits, including anti-inflammatory and anti-apoptosis effects. It also exhibits neuroprotective effects in Alzheimer’s disease (AD) via the ROS-JNK-p53 pathway. However, it is not clear if it has neuroprotective effects against cognitive impairment in Parkinson’s disease (PD). Through network pharmacology, we identified probable targets as well as signal pathways through which PF might affect cognitive impairment in PD. Then, we experimentally validated our findings. The core genes of the PPI network include MAPK8 (JNK), TP53, CASP3 (caspase-3), protein-95 (PSD95), and SYN. Pathway enrichment analysis revealed that genes involved in apoptosis and MAPK signaling were significantly enriched. Because JNK is a key mediator of p53-induced apoptosis, we wondered if JNK/p53 pathway influences the effects of PF against apoptosis in mouse model of PD. Molecular docking analysis showed that PF had good affinity for JNK/p53. The results of the experiments indicated that PF ameliorated behavioral impairments and upregulated the expression of the dopamine (DA) neurons, suppressed cell apoptosis in substantia nigra pars compacta (SNpc) of PD. Additionally, PF improved MPTP-induced neuronal injury by inhibiting apoptosis in hippocampal neurons of the CA1 and CA3, and upregulating postsynaptic density PSD95 as well as synaptophysin (SYN) protein levels. Similar protective effects were observed upon JNK/p53 pathway inhibition using SP600125. Overall, PF improved cognitive impairment in PD by inhibiting JNK/p53 signaling pathway.

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“…The JNK signaling pathway can activate downstream p53 signaling pathways [27][28][29]. Thus, we also examined the protein levels of p53 protein and its target genes in NPCs.…”

Section: Discussionmentioning

confidence: 99%

Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway

Cheng

Yuan

et al. 2020

Int. J. Biol. Sci.

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Syndecan-4 is a member of the polysaccharide syndecan family and plays a vital role in intervertebral disc development. Several studies have demonstrated the positive relationship between syndecan-4 expression and intervertebral disc degeneration. However, the detailed molecular mechanism by which syndecan-4 affects the degeneration of nucleus pulposus cells (NPCs) remains unclear. In this study, cell viability was determined by CCK-8 assay, mRNA level was determined by qPCR, and protein expression was determined by western blot. Molecular interaction was determined by chromatin immunoprecipitation assay. A rabbit intervertebral disc degeneration model was established to test for syndecan in vivo. We found that the morphology and viability of NPCs were not affected by the expression of syndecan-4 in the long term. While the NPC function were affected, which results in the degeneration of intervertebral disc. Syndecan-4 overexpression promoted the degeneration of NPCs. Syndecan-4 also activated the JNK signaling pathway and downstream p53 pathways, and promoted degeneration. Inhibition of the JNK pathway, which down-regulated p53 expression, alleviated the degeneration. In an in vivo study, syndecan-4 siRNA injection stopped the development of rabbit disc degeneration, and even created a reverse effect, in which JNK/p53 played a role. Syndecan-4 may be a novel therapeutic target for intervertebral disc degeneration via suppressing the JNK/p53 pathway.

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Role of JNK and Involvement of p53 in Stimulation of Growth Potential Realization of Mesenchymal Precursor Cells by Alkaloid Songorine

Cited by 9 publications

References 15 publications

Paeoniflorin ameliorates cognitive impairment in Parkinson’s disease via JNK/p53 signaling

Paeoniflorin ameliorates cognitive impairment in Parkinson’s disease via JNK/p53 signaling

Paeoniflorin Ameliorates Cognitive Impairment in Parkinson’s Disease via JNK/p53 Signaling

Syndecan-4 is a Novel Therapeutic Target for Intervertebral Disc Degeneration via Suppressing JNK/p53 Pathway

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