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Protein arginine methyltransferase-1 stimulates dopaminergic neuronal cell death in a Parkinson's disease model
- Source :
- Biochemical and biophysical research communications. 530(2)
- Publication Year :
- 2020
-
Abstract
- Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.
- Subjects :
- 0301 basic medicine
Male
Programmed cell death
Protein-Arginine N-Methyltransferases
Parkinson's disease
Biophysics
Substantia nigra
Biology
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Dopaminergic Cell
medicine
Animals
Humans
Molecular Biology
Cell Death
Pars compacta
MPTP
Dopaminergic Neurons
Dopaminergic
Parkinson Disease
Cell Biology
Rotenone
medicine.disease
Cell biology
Disease Models, Animal
030104 developmental biology
nervous system
chemistry
030220 oncology & carcinogenesis
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 530
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....3cd555773b339b756ec8d2edf3dc12b5