Alteration in long noncoding RNAs in response to oxidative stress and ladostigil in SH-SY5Y cells
bioRxiv(2022)
Abstract
Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2– related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.
### Competing Interest Statement
The authors have declared no competing interest.
* AD
: Alzheimer’s disease
CNS
: central nerve system
DE
: differentially expressed
ER
: endoplasmic reticulum
FACS
: fluorescence-activated cell sorting
FC
: fold change
FCS
: fetal calf serum
FDR
: false discovery rate
H2O2
: hydrogen peroxide
MBS
: miRNA binding site
MEM
: minimum essential medium
NT
: not treated
Nrf2
: nuclear factor erythroid 2-related factor 2
O2−
: superoxide anion
ONOO−
: peroxynitrite
PD
: Parkinson’s disease
PI
: propidium iodide
PS
: phosphatidylserine
I/R
: ischemia and reperfusion
RNS
: reactive nitrogen species
ROS
: reactive oxygen species
TF
: transcription factor
TMM
: trimmed mean of M-values
MoreTranslated text
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined