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.
Cell Biochem Funct
; 38(8): 1025-1035, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-32474958
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson Secundaria
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Factor I del Crecimiento Similar a la Insulina
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1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina
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Fármacos Neuroprotectores
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MicroARNs
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Óxido Nítrico Sintasa de Tipo II
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Biochem Funct
Año:
2020
Tipo del documento:
Article
País de afiliación:
China