The Effect of SPTLC2 on Promoting Neuronal Apoptosis is Alleviated by MiR-124-3p Through TLR4 Signalling Pathway
- 51 Downloads
To investigate the role and mechanism of microRNA-124-3p (miR-124-3p) and serine palmitoyltransferase long chain base subunit 2 (SPTLC2) in neuronal apoptosis induced by mechanical injury. Transient transfection was used to modify the expression of miR-124-3p and SPTLC2. After transfection, neuronal apoptosis was evaluated in an in vitro injury model of primary neurons using TUNEL staining and western blot. The correlation between miR-124-3p and SPTLC2 was identified through a dual luciferase reporter assay in HEK293 cells. A rescue experiment in primary neurons was performed to further confirm the result. To explore the downstream mechanisms, co-immunoprecipitation was performed to identify proteins that interact with SPTLC2 in toll-like receptor 4 (TLR4) signalling pathway. Subsequently, the relative expression levels of TLR4 pathway molecules were measured by western blot. Our results showed that increased miR-124-3p can inhibit neuronal apoptosis, which is opposite to the effect of SPTLC2. In addition, miR-124-3p was proved to negatively regulate SPTLC2 expression and suppress the apoptosis-promoting effect of SPTLC2 via the TLR4 signalling pathway.
KeywordsmiR-124-3p SPTLC2 Apoptosis TLR4
This study was supported by the Natural Science Foundation of China (No. 81471264).
Compliance with Ethical Standards
Conflict of interest
The authors have no conflicts of interest to disclose.
- 4.Huang S, Ge X, Yu J, Han Z, Yin Z, Li Y, Chen F, Wang H, Zhang J, Lei P (2018) Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. Faseb J 32(1):512–528CrossRefGoogle Scholar
- 14.Rotthier A, Auer-Grumbach M, Janssens K, Baets J, Penno A, Almeida-Souza L, Van Hoof K, Jacobs A, De Vriendt E, Schlotter-Weigel B, Loscher W, Vondracek P, Seeman P, De Jonghe P, Van Dijck P, Jordanova A, Hornemann T, Timmerman V (2010) Mutations in the SPTLC2 subunit of serine palmitoyltransferase cause hereditary sensory and autonomic neuropathy type I. Am J Hum Genet 87(4):513–522CrossRefGoogle Scholar
- 32.Jazvinšćak Jembrek M, Hof PR, Šimić G (2015) Ceramides in Alzheimer's Disease: key mediators of neuronal apoptosis induced by oxidative stress and abeta accumulation. Oxid Med Cell Longev 2015:346783Google Scholar