摘要
Parkinson's disease(PD) is a common age-related degenerative disease of the central nervous system caused by hereditary,pesticides,metals,and polychlorinated biphenyls.Paraquat(PQ),a widely used herbicide,causes PD.Long noncoding RNAs(lncRNAs) are nonprotein-coding transcripts,expressed in the brain and play irreplaceable roles in neurodegenerative diseases.Nrf2 is an important genetic transcription regulator in oxidative stress.We aimed to discover novel PQ or MPTP-Nrf2-related lncRNAs and explore their associations with PD.First,a IncRNA array was used to identify 17157 lncRNAs and 13707 mRNAs on a Mouse LncRNA Expression Microarray(fold change ≥2,p-value<0.05).Then,several lncRNAs were double-checked using real-time quantitative reverse transcription PCR(qRT-PCR) and fluorescence in situ hybridization.Coding-noncoding analysis and qRT-PCR were applied to discover the functions of lncRNAs and predict the targeted genes.In vivo,PQ and1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) exposure changed the IncRNA expression profiles,probably related to their neurotoxic mechanism.The changes in their IncRNA expression were distinct but related.PQ changed the IncRNA expression profiling in the substantia nigra(SN) through an interaction with Nrf2,thus changing the NR_027648/Zc3hl4/Cybb and NR_030777/Zfp326/Cpne5 mRNA pathways.Similarly,MPTP changed the IncRNA expression profiling in SN through an interaction with Nrf2.Nrf2 may be involved in the development of neurodegeneration induced by PQ and MPTP via interactions of lncRNAs as the molecular mechanism.Our findings,for the first time,indicate the potential roles of lncRNAs in the development of PD by PQ or MPTP and provide positive insights into future mechanism studies.
Parkinson's disease(PD) is a common age-related degenerative disease of the central nervous system caused by hereditary,pesticides,metals,and polychlorinated biphenyls.Paraquat(PQ),a widely used herbicide,causes PD.Long noncoding RNAs(lncRNAs) are nonprotein-coding transcripts,expressed in the brain and play irreplaceable roles in neurodegenerative diseases.Nrf2 is an important genetic transcription regulator in oxidative stress.We aimed to discover novel PQ or MPTP-Nrf2-related lncRNAs and explore their associations with PD.First,a IncRNA array was used to identify 17157 lncRNAs and 13707 mRNAs on a Mouse LncRNA Expression Microarray(fold change ≥2,p-value<0.05).Then,several lncRNAs were double-checked using real-time quantitative reverse transcription PCR(qRT-PCR) and fluorescence in situ hybridization.Coding-noncoding analysis and qRT-PCR were applied to discover the functions of lncRNAs and predict the targeted genes.In vivo,PQ and1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) exposure changed the IncRNA expression profiles,probably related to their neurotoxic mechanism.The changes in their IncRNA expression were distinct but related.PQ changed the IncRNA expression profiling in the substantia nigra(SN) through an interaction with Nrf2,thus changing the NR_027648/Zc3hl4/Cybb and NR_030777/Zfp326/Cpne5 mRNA pathways.Similarly,MPTP changed the IncRNA expression profiling in SN through an interaction with Nrf2.Nrf2 may be involved in the development of neurodegeneration induced by PQ and MPTP via interactions of lncRNAs as the molecular mechanism.Our findings,for the first time,indicate the potential roles of lncRNAs in the development of PD by PQ or MPTP and provide positive insights into future mechanism studies.
引文