ABSTRACT
As widely reported, dysregulated ferroptosis is closely associated with Parkinson's disease (PD) progression. The goal of the present study was to probe the roles of long noncoding RNA (lncRNA) nuclear enriched assembly transcript 1 (NEAT1) in regulating ferroptosis in PD. PD cell model was constructed by subjecting SKNSH cells to 1methyl4phenylpyridinium (MPP+) for 24 h. The RNA levels of NEAT1, miRNA (miR)1505p, and BRCA1associated protein 1 (BAP1) were evaluated using qRTPCR. The protein levels of glutathione peroxidase 4 (GPX4), BAP1, and solute carrier family 7 member 11 (SLC7A11) were determined using western blot. Cell viability was assessed using 3(4,5dimethylthiazolyl2)2, 5diphenyltetrazolium bromide (MTT) assay. In addition, fluorescent probe 2,7dichlorodihydrofluorescein diacetate (DCFHDA) was employed to determine the ROS level. Moreover, the levels of GSH, MDA, and Fe2+ were also measured. Finally, the interactions among NEAT1, miR1505p, and BAP1 were identified by dual luciferase reporter gene assay, and/or RIP assay. Upregulated NEAT1 was observed in PD cell model. Knockdown of NEAT1 elevated viability and GSH level in PD cell model and reduced ROS, MDA, and Fe2+ levels. Moreover, NEAT1 functioned as a sponge to suppress miR1505p expression. Moreover, miR1505p overexpression suppressed ferroptosis in PD cell model. We subsequently found that miR1505p regulated SLC7A11 expression by directly binding to BAP1. miR1505p inhibition or BAP1 overexpression mitigated the antiferroptosis effect meditated by shNEAT1. Taken together, knockdown of NEAT1 mitigated MPP+induced ferroptosis through regulating BAP1/SLC7A11 axis by sponging miR1505p, indicating the potential of NEAT1 as a promising therapeutic target for PD.
Subject(s)
MicroRNAs , RNA, Long Noncoding , 1-Methyl-4-phenylpyridinium/toxicity , Cell Line, Tumor , MicroRNAs/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Reactive Oxygen SpeciesABSTRACT
The net greenhouse gas emissions from upland soils, as indicated by global warming potential (GWP), mainly depend on the soil carbon sequestration and nitrous oxide (N2O) emissions. The annual changes in surface (0-20 cm) soil organic carbon (SOC) content from 2010 to 2017 and the N2O emissions from 2014 to 2017 were measured within a long-term fertilization experiment. The objective was to quantify the effect of stalk incorporation on the soil carbon sequestration, annual N2O emissions, and GWP of a winter wheat-summer maize field in the Guanzhong Plain. The field experiment included three treatments:conventional fertilization (CF), conventional fertilization plus maize stalks (CFS), and an unfertilized control (CK). The CF and CFS treatments received the same amount of urea per year, with nitrogen (N) input at 165 kg·hm-2 and 188 kg·hm-2 in the winter wheat season and summer maize season, respectively. The CF treatment retained the stubbles (about 10 cm above ground) when harvesting the winter wheat and summer maize crops. The CFS treatment retained the same wheat stubbles and all maize stalks (containing approximately 40 kg·hm-2 of N). The CK treatment was unfertilized throughout the year, with the stubble management the same as that in the CF treatment. The results showed that the CK treatment displayed few changes in SOC content and low N2O emissions, with GWP varying from 0.04 to 0.11 t·(hm2·a)-1. The SOC contents in the CF and CFS treatments increased linearly with the fertilization years (P<0.001), and their SOC sequestration rates were 0.69 t·(hm2·a)-1 and 0.97 t·(hm2·a)-1, respectively. The N2O emissions from the CF and CFS treatments varied from 1.65 to 5.36 kg·(hm2·a)-1 and from 3.08 to 7.73 kg·(hm2·a)-1, respectively. The annual N2O emissions from the CFS treatment were 43%-94% higher than those from the CF treatment, whereas the difference was only significant between 2015 and 2016 (P<0.05). The GWP of the CF and CFS treatments varied from -1.95 to -0.28 t·(hm2·a)-1 and from -2.59 to -0.35 t·(hm2·a)-1, respectively. The cumulative GWP of the CFS treatment was 42% lower than that of the CF treatment between 2014 and 2017. In summary, the studied winter wheat-summer maize field acted as a sink of greenhouse gases under the conventional fertilization regime. The stalk incorporation further favored greenhouse gas mitigation despite the trade-offs between SOC sequestration and N2O emissions.