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Hydrogen sulfide protects against TNF-α induced neuronal cell apoptosis through miR-485-5p/TRADD signaling
Zhiqiang Chen1, Zhonghe Zhang2, Dongdong Zhang3
1Department of Orthopedic Surgery, Liaocheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, China.
Background And Objective:
Increasing studies suggest that miRNAs are served as responders and regulators for pathological change in human. miR-485-5p is such a miRNA that has been proved to be affected by spinal cord I/R injury. This study was to investigate the functional involvement and mechanism of miR-485-5p in sulfuretted hydrogen (H2S) protecting neural cell from injury.
Methods:
In this study, serum tumor necrosis factor (TNF-α) and miR-485-5p were detected in 20 patients with spinal cord ischemia/reperfusion (I/R) injury and in 20 healthy control. H2S was administered by GYY4137 treatment. Two TNF-α-stimulated neural human cell lines, AGE1.HN and SY-SH-5Y, were used for in vitro I/R experiments. Quantitative RT-PCR was performed to determine miR-485-5p expression. QRT-PCR and western blot were respectively performed to evaluate expression of tumor necrosis factor receptor type 1-associated DEATH domain protein (TRADD).
Results:
The result showed that serum TNF-α was significantly reduced in patients compared with healthy control. In vitro TNF-α treatment dose dependently caused GE1.HN and SY-SH-5Y apoptosis, whereas this promotion action was reversed by CYY4137. Moreover, we found that H2S protected neuronal cell against apoptosis via TRADD dependent. By luciferase reporting gene assay, western blot and qRT-PCR, we confirmed that TRADD expression was regulated by miR-485-5p. Such miR-485-5p/TRADD axis was proved to be involved in GE1.HN and SY-SH-5Y neural cell-protective process of H2S.
Conclusion:
In summary, our data for the first time identifies miR-485-5p/TRADD axis in hydrogen sulfide protecting against TNF-α-induced neuronal cell apoptosis.
Insights
Hydrogen sulfide (H2S) protects neural cells from injury by regulating miR-485-5p and TRADD. This study reveals the miR-485-5p/TRADD axis involved in H2S-mediated neuroprotection against TNF-α-induced apoptosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- MicroRNAs (miRNAs) regulate pathological changes in humans.
- miR-485-5p is affected by spinal cord ischemia/reperfusion (I/R) injury.
- Hydrogen sulfide (H2S) shows neuroprotective potential.
Purpose of the Study:
- Investigate the role of miR-485-5p in H2S-mediated neuroprotection.
- Elucidate the mechanism of H2S in protecting neural cells from injury.
- Determine the involvement of the miR-485-5p/TRADD axis in H2S neuroprotection.
Main Methods:
- Detected serum TNF-α and miR-485-5p in spinal cord I/R patients and controls.
- Administered H2S using GYY4137 treatment in vitro.
- Utilized quantitative RT-PCR, western blot, and luciferase reporter assays to analyze gene expression and protein interactions.
Main Results:
- Serum TNF-α was reduced in I/R patients.
- H2S (GYY4137) reversed TNF-α-induced neuronal apoptosis in vitro.
- H2S protected neuronal cells via a TRADD-dependent pathway.
- miR-485-5p was confirmed to regulate TRADD expression.
- The miR-485-5p/TRADD axis was involved in H2S neuroprotection.
Conclusions:
- Identified the miR-485-5p/TRADD axis in H2S neuroprotection.
- Demonstrated H2S protects against TNF-α-induced neuronal apoptosis.
- Established the mechanism of H2S neuroprotection involving miR-485-5p and TRADD.
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