MiR‐302b‐5p enhances the neuroprotective effect of IGF‐1 in methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced Parkinson's disease by regulating inducible nitric‐oxide synthase

Abstract

Parkinson's disease (PD) is a neurodegenerative disease which results in damage in neuronal cells. Insulin-like growth factor (IGF)-1 was previously reported to play a role of neuroprotection in some diseases. Nitric oxide (NO) can also regulate neuronal cells. However, the mechanisms underlying IGF-1 and NO in PD still need to be elucidated. In present study, we explored the interaction between IGF-1 and inducible Nitric-Oxide Synthase (iNOS) in PD progression. We firstly constructed PD models by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or MPP + treatment. Then RT-qPCR revealed that IGF-1 expression was downregulated while iNOS expression was upregulated in MPTP model. Moreover, IGF-1 elevation or iNOS depletion enhanced cell viability and blocked cell apoptosis. Rescue assay disclosed iNOS overexpression reversed the effect on viability and apoptosis mediated by IGF-1 upregulation. Furthermore, IGF-1 was identified to positively regulate miR-302b-5p which could target iNOS. MiR-302b-5p could abolish the inhibitory function IGF-1 exerted on cell apoptosis and iNOS could counteract miR-302b-5p upregulation-triggered inhibition on cell apoptosis as well. Besides, we observed the deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice. To sum up, present study proved that miR-302b-5p enhanced the neuroprotective effect of IGF-1 in MPTP-induced PD by regulating iNOS, recommending a novel therapeutic target for PD treatment. Significance of the study: In this study, we mainly explored that IGF-1 was decreased while iNOS was boosted in MPTP-induced PD mice model; IGF-1 suppressed while iNOS promoted MPP +-induced toxicity and apoptosis in SH-SY5Y cells; miR-302b-5p ehanhced the neuroprotective effect of IGF-1 via targeting Inos; deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice.

Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer

“…miRNA can regulate arginine metabolism by regulating the expression of key molecules in arginine metabolism pathway, such as ASS ( Bates et al, 2010 ; Tu et al, 2020 ), ARG1 ( Bates et al, 2010 ; Yoo et al, 2019 ), ARG2 ( Dunand-Sauthier et al, 2014 ; Jin et al, 2014 ; Kim et al, 2017 ; Wang Y. et al, 2017 ), CAT-1 ( Chang et al, 2004 ; Li Y. et al, 2018 ), ODC ( Jagannathan et al, 2015 ) and NOS ( Perske et al, 2010 ; Yan et al, 2011 ; Guo et al, 2012 ; Sun et al, 2012 ; Zhu et al, 2013 ; Li et al, 2014 , 2017 , Li H.T. et al, 2018 ; Fu et al, 2015 ; Jiang et al, 2015 ; Zhang et al, 2015 , 2020 ; Rasheed et al, 2016 ; Reilly et al, 2016 ; Muxel et al, 2017 , 2018 ; Wang C. et al, 2017 , Wang et al, 2019 ; Cui et al, 2020 ; Lin et al, 2020 ; Scalavino et al, 2020 ; Table 1 ). It has been found that multiple miRNAs could target the same enzyme or transporter protein, and the same molecule could also be regulated by multiple miRNAs.…”

Optimization of N-Phenylpropenoyl-l-amino Acids as Potent and Selective Inducible Nitric Oxide Synthase Inhibitors for Parkinson’s Disease

“…MPTP remarkably induces DAergic neuron loss by activating the iNOS/NO/pathway in microglia cells, which results in the reduction of DA levels . Results showed that MPTP remarkably increased the NO level and decreased the DA level in the SNpc and striatum (STR) compared with the control group.…”

“…MPTP remarkably induces DAergic neuron loss by activating the iNOS/NO/pathway in microglia cells, which results in the reduction of DA levels. 28 Results showed that MPTP remarkably increased the NO level and decreased the DA level in the SNpc and striatum (STR) compared with the control group. However, pre-treatment with 18 remarkably decreased the NO level and increased the DA level in the SNpc and STR compared with the MPTP group (Figure 8A,B).…”

MicroRNA‑29‑3p regulates the β‑catenin pathway by targeting IGF1 to inhibit the proliferation of prolactinoma cells

“…The results of the present study suggested that inhibition of IGF-1 by exogenous methods could inhibit the growth of prolactinoma and reduce the secretion of PRL and GH. In vivo, IGF-1 is also targeted by miRNAs (31,32). In polycystic ovary syndrome, IGF-1 is targeted by miR-323-3p and miR-323-3p/IGF-1 is involved in the regulation of steroid secretion and human cumulus cell function (33).…”